Publications by authors named "Vahid Salimi"

49 Publications

The pro-apoptosis effects of Echinacea purpurea and Cannabis sativa extracts in human lung cancer cells through caspase-dependent pathway.

BMC Complement Med Ther 2021 Jan 14;21(1):37. Epub 2021 Jan 14.

Department of Biochemistry, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Background: Considering the advantages of using medicinal herbs as supplementary treatments to sensitize conventional anti-cancer drugs, studying functional mechanisms and regulatory effects of Echinacea purpurea (as a non-cannabinoid plant) and Cannabis sativa (as a cannabinoid plant) are timely and required. The potential effects of such herbs on lung cancer cell growth, apoptosis, cell cycle distribution, cellular reactive oxygen species (ROS) level, caspase activity and their cannabinomimetic properties on the CB2 receptor are addressed in the current study.

Methods: The cytotoxic effect of both herb extracts on the growth of lung cancer cells (A549) was assessed using the MTT assay. The annexin-V-FITC staining and propidium iodide (PI) staining methods were applied for the detection of apoptosis and cell cycle distribution using flow cytometry. The cellular level of ROS was measured using 7'-dichlorofluorescin diacetate (DCFH-DA) as a fluorescent probe in flow cytometry. The caspase 3 activity was assessed using a colorimetric assay Kit.

Results: Echinacea purpurea (EP) root extract induced a considerable decrease in A549 viable cells, showing a time and dose-dependent response. The cell toxicity of EP was accompanied by induction of early apoptosis and cell accumulation at the sub G1 phase of the cell cycle. The elevation of cellular ROS level and caspase 3 activity indicate ROS-induced caspase-dependent apoptosis following the treatment of A549 cells by EP extract. The observed effects of EP extract on A549 growth and death were abrogated following blockage of CB2 using AM630, a specific antagonist of the CB2 receptor. Increasing concentrations of Cannabis sativa (CS) induced A549 cell death in a time-dependent manner, followed by induction of early apoptosis, cell cycle arrest at sub G1 phase, elevation of ROS level, and activation of caspase 3. The CB2 blockage caused attenuation of CS effects on A549 cell death which revealed consistency with the effects of EP extract on A549 cells.

Conclusions: The pro-apoptotic effects of EP and CS extracts on A549 cells and their possible regulatory role of CB2 activity might be attributed to metabolites of both herbs. These effects deserve receiving more attention as alternative anti-cancer agents.
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http://dx.doi.org/10.1186/s12906-021-03204-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809807PMC
January 2021

Survey of BK Virus in Renal Transplant Recipients in Iran: A Systematic Review and Meta-Analysis.

Intervirology 2020 Dec 17:1-9. Epub 2020 Dec 17.

Virology Department, School of Public Health, Tehran University of Medical Sciences, Teheran, Iran,

Introduction: BK virus (BKV) infection in renal transplant (RT) recipients can cause hemorrhagic cystitis, transient renal dysfunction, and BKV nephropathy (BKVN). The prevalence and significance of BKV in RT recipients remain to be clarified in the Iranian population. The purpose of this review is to summarize the overall prevalence of BKV infection in RT recipients from previously published studies in Iran.

Methods: We systematically reviewed articles through a comprehensive search of the main electronic and Persian national databases up to November 2019.

Results: The overall pooled prevalence of BKV infection among the Iranian population was 23% (95% CI; 15-33%). Comparing these studies revealed that the prevalence of BKV in plasma samples ranges from 3 to 40%, in renal biopsies 1-13%, and in urine samples 10-49%. Due to substantial heterogeneity among reported studies (I2 = 93%, p < 0.01), random-effect meta-analysis was performed. BKV infection rate was slightly higher in women than men (16%, p = 0.04 vs. 14%, p < 0.01, respectively). The majority of the studies employed real-time PCR (24%, I2 = 93, p < 0.01) and analyzed plasma samples alone or in combination with other types of specimens. BKV prevalence from 5 cities among the Iranian population showed a higher prevalence rate in Guilan.

Conclusion: Our analysis provides a preliminary estimate of the epidemiology of BKV infection in RT recipients in Iran. These results arouse a need for more epidemiological studies of BKV infection in different unanalyzed regions in Iran. Early detection of BKV in RT recipients helps timely nephropathy diagnosis and prevents graft loss.
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http://dx.doi.org/10.1159/000512132DOI Listing
December 2020

Global burden of acute lower respiratory infection associated with human metapneumovirus in children under 5 years in 2018: a systematic review and modelling study.

Lancet Glob Health 2021 01 26;9(1):e33-e43. Epub 2020 Nov 26.

Centre for Global Health, Usher Institute, Edinburgh Medical School, University of Edinburgh, Edinburgh, UK. Electronic address:

Background: Human metapneumovirus is a common virus associated with acute lower respiratory infections (ALRIs) in children. No global burden estimates are available for ALRIs associated with human metapneumovirus in children, and no licensed vaccines or drugs exist for human metapneumovirus infections. We aimed to estimate the age-stratified human metapneumovirus-associated ALRI global incidence, hospital admissions, and mortality burden in children younger than 5 years.

Methods: We estimated the global burden of human metapneumovirus-associated ALRIs in children younger than 5 years from a systematic review of 119 studies published between Jan 1, 2001, and Dec 31, 2019, and a further 40 high quality unpublished studies. We assessed risk of bias using a modified Newcastle-Ottawa Scale. We estimated incidence, hospital admission rates, and in-hospital case-fatality ratios (hCFRs) of human metapneumovirus-associated ALRI using a generalised linear mixed model. We applied incidence and hospital admission rates of human metapneumovirus-associated ALRI to population estimates to yield the morbidity burden estimates by age bands and World Bank income levels. We also estimated human metapneumovirus-associated ALRI in-hospital deaths and overall human metapneumovirus-associated ALRI deaths (both in-hospital and non-hospital deaths). Additionally, we estimated human metapneumovirus-attributable ALRI cases, hospital admissions, and deaths by combining human metapneumovirus-associated burden estimates and attributable fractions of human metapneumovirus in laboratory-confirmed human metapneumovirus cases and deaths.

Findings: In 2018, among children younger than 5 years globally, there were an estimated 14·2 million human metapneumovirus-associated ALRI cases (uncertainty range [UR] 10·2 million to 20·1 million), 643 000 human metapneumovirus-associated hospital admissions (UR 425 000 to 977 000), 7700 human metapneumovirus-associated in-hospital deaths (2600 to 48 800), and 16 100 overall (hospital and community) human metapneumovirus-associated ALRI deaths (5700 to 88 000). An estimated 11·1 million ALRI cases (UR 8·0 million to 15·7 million), 502 000 ALRI hospital admissions (UR 332 000 to 762 000), and 11 300 ALRI deaths (4000 to 61 600) could be causally attributed to human metapneumovirus in 2018. Around 58% of the hospital admissions were in infants under 12 months, and 64% of in-hospital deaths occurred in infants younger than 6 months, of which 79% occurred in low-income and lower-middle-income countries.

Interpretation: Infants younger than 1 year have disproportionately high risks of severe human metapneumovirus infections across all World Bank income regions and all child mortality settings, similar to respiratory syncytial virus and influenza virus. Infants younger than 6 months in low-income and lower-middle-income countries are at greater risk of death from human metapneumovirus-associated ALRI than older children and those in upper-middle-income and high-income countries. Our mortality estimates demonstrate the importance of intervention strategies for infants across all settings, and warrant continued efforts to improve the outcome of human metapneumovirus-associated ALRI among young infants in low-income and lower-middle-income countries.

Funding: Bill & Melinda Gates Foundation.
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http://dx.doi.org/10.1016/S2214-109X(20)30393-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783516PMC
January 2021

Neutrophils in respiratory syncytial virus infection: From harmful effects to therapeutic opportunities.

Br J Pharmacol 2021 Feb 15;178(3):515-530. Epub 2020 Dec 15.

Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Respiratory syncytial virus (RSV) is an important infectious agent in infants and young children. In most cases, RSV infection only causes mild disease, but in some, it requires invasive ventilation. Although antiviral drugs are obvious candidates to treat viral illness, and some have shown antiviral effects in humans, antivirals such as GS-5806, ALX-0171 and ALS-8176 have not yet met their expectations. Since the inappropriate or dysregulated immune response against RSV leads to harmful immune pathology, a robust immune cascade is probably underway by the time patients reach the hospital. RSV infection is associated with a strong neutrophil influx into the airway. It not clear if these cells contribute to antiviral defence or to lung pathology. This article discusses the protective and harmful roles of neutrophils during RSV infection and provides an overview of mechanisms by which neutrophil function could be targeted to prevent tissue injury and preserve homeostasis.
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http://dx.doi.org/10.1111/bph.15318DOI Listing
February 2021

First Cases of SARS-CoV-2 in Iran, 2020: Case Series Report.

Iran J Public Health 2020 Aug;49(8):1564-1568

Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

In Jan 2020, the outbreak of the 2019 novel coronavirus (SARS-CoV-2) in Wuhan, Hubei Province of China spread increasingly to other countries worldwide which WHO declared it as a public health emergency of international concern. Iran was included in the affected countries. Throat swab specimens were collected and tested by using real-time reverse transcription PCR (RT-PCR) kit targeting the E region for screening and RNA dependent RNA polymerase for confirmation. Conventional RT-PCR was conducted for the N region and the PCR products were sequenced by Sanger sequencing. The first seven cases of SARS-CoV-2 infections were identified in Qom, Iran. This report describes the clinical and epidemiological features of the first cases of SARS-CoV-2 confirmed in Iran. Future research should focus on finding the routes of transmission for this virus, including the possibility of transmission from foreign tourists to identify the possible origin of SARS-CoV-2 outbreak in Iran.
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http://dx.doi.org/10.18502/ijph.v49i8.3903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554384PMC
August 2020

Frequent detection of enterovirus D68 and rhinovirus type C in children with acute respiratory infections.

Eur J Clin Microbiol Infect Dis 2021 Mar 3;40(3):637-642. Epub 2020 Oct 3.

Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, 1471613151, Iran.

This study aimed to evaluate the prevalence of human rhinoviruses (HRVs) and the emergence of enterovirus D68 (EV-D68) in children. A total of 322 nasopharyngeal swab samples were provided from children with an initial diagnosis of upper and lower respiratory tract infections. A total of 34 and 70 cases were positive for EV-D68 and HRV, respectively. The phylogenetic analysis revealed that the clades A and B are the prevalent genotypes for EV-D68 and the HRV-positive samples belong to three types including HRV-A, HRV-B, and HRV-C. The results showed that EV-D68 and HRV-C are circulating in Iran especially in the winter.
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http://dx.doi.org/10.1007/s10096-020-04051-yDOI Listing
March 2021

Opioids/cannabinoids as a potential therapeutic approach in COVID-19 patients.

Expert Rev Respir Med 2020 10 30;14(10):965-967. Epub 2020 Jun 30.

Department of Virology, School of Public Health, Tehran University of Medical Sciences , Tehran, Iran.

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http://dx.doi.org/10.1080/17476348.2020.1787836DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7441794PMC
October 2020

The local and circulating SOX9 as a potential biomarker for the diagnosis of primary bone cancer.

J Bone Oncol 2020 Aug 31;23:100300. Epub 2020 May 31.

Department of Biochemistry, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Purpose: The status of the local and circulating SOX9, a master regulator of the tumor fate, and its relevance to tumor types, severity, invasion feature, response to therapy, and chemotherapy treatment were surveyed in bone cancer in the current study.

Methods: The expression level was evaluated in tissue and peripheral blood mononuclear cells from patients with different types of malignant and benign bone tumors also tumor margin tissues using Real-Time PCR. The protein level of SOX9 was assessed using immunohistochemistry and western blot analysis. Also, the correlations of the expression level with the patient's clinical and pathological features were considered.

Results: The remarkable overexpression of was detected in bone tumors compared to tumor margin tissues ( < 0.0001). Malignant bone tumors revealed a higher expression of compared to benign tumors ( < 0.0001) while osteosarcoma tumors showed higher expression levels compared to Ewing sarcoma, and chondrosarcoma. Overexpression of was observed in high grade, metastatic, recurrent tumors also tumors with poor response to therapy. Besides, the patients under the chemotherapy treatment demonstrated higher levels of compared to the rest of malignant tumors ( = 0.02). The simultaneous up-regulation of circulating in the patients with bone cancer was observed compared to healthy individuals ( < 0.0001) accompanying with overexpression of in malignant tumors compared to benign tumors (P < 0.0001). The circulating expression was up-regulated in the patients with malignant bone tumors who receive chemotherapy treatment also patients with high grade, metastatic, recurrent tumors. The protein level of SOX9 was in line with our data on the gene expression.

Conclusion: The simultaneous overexpression of local and circulating SOX9 in bone cancer besides its positive correlation with tumor severity, malignancy, size, and chemotherapy may deserve receiving more attention in bone cancer diagnosis and therapy.
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http://dx.doi.org/10.1016/j.jbo.2020.100300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7292907PMC
August 2020

P16INK4A Immunohistochemistry as a Gold Standard for Cervical Cancer and Precursor Lesions Screening.

Iran J Public Health 2020 Feb;49(2):312-322

Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Background: High-risk (HR) Human papillomaviruses (HPVs) are known as the main factors implicated in the pathogenesis of cervical preinvasive and invasive lesions. Therefore, the presence or absence of HR-HPV can be followed for the prognosis of low-grade and high-grade squamous intraepithelial lesions. Since the overexpression of p16INK4a protein depends on the presence of transcriptionally-active HPV, and due to its availability and simple interpretation, it may be considered as a proper marker to diagnose cervical cancer.

Methods: An immunohistochemical analysis of p16INK4a was performed in 72 cervical tissue specimens at Imam Khomeini Complex Hospital (Tehran, Iran) from 2016 to 2018. The performance parameters were calculated and compared using receiving operating characteristics curve (ROC) details.

Results: p16INK4a is significantly up-regulated in the cervical cancer samples in comparison with that in normal samples. Moreover, the ROC data showed the potential ability of p16INK4a under determined conditions as a diagnostic marker for CIN 2-3 staging and invasive cervical cancer. The molecular typing disclosed the attendance of HPV DNA in 44.4% of cases (32/72) with a predominance of HPV type 16.

Conclusion: The molecular biomarker p16INK4a can be a good candidate for the early diagnosis and prognosis of cervical cancer in HPV-infected patients. Considering the increase in the expression level of p16INK4a in cancer and precancer tissues, p16INK4a may be used for early detection of cervical cancer.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231710PMC
February 2020

Potential of H1N1 influenza A virus as an air borne pathogen to induce infectivity in pancreas: a mouse model study.

J Environ Health Sci Eng 2020 Jun 17;18(1):303-310. Epub 2020 Mar 17.

1Virology Department, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Introduction: H1N1 influenza virus, as an indoor/outdoor pathogen in air, can cause the flu-like illness and respiratory complication. The aim of this study was to evaluate the H1N1 influenza virus replication in pancreas and investigate the immune response against infected pancreas.

Material And Methods: First, mouse pancreas cell line was infected by H1N1 influenza A virus using intranasally and intravenously infection methods, and then the pancreas tissue was collected and pathology experiment was carried out. Next, the protein and genome of influenza virus were detected using immunocytochemistry and real-time PCR, respectively. In addition, serum cytokines and serum lipase were investigated using ELISA.

Result: The in-vitro results proved that the mouse pancreatic cell line can support influenza virus replication. The result also proved that influenza virus is capable to infect pancreas and induce pancreas damage. Further, the immune response in mice with infected pancreas exhibited a completely different pattern with that of mice infected through intranasal method.

Conclusion: It can be concluded that influenza virus can infect pancreas and change the influenza disease pathway, which might result in a pancreatic injury.
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http://dx.doi.org/10.1007/s40201-020-00468-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7203352PMC
June 2020

Cyclooxygenase enzyme and PGE2 expression in patients with functional and non-functional pituitary adenomas.

BMC Endocr Disord 2020 Mar 14;20(1):39. Epub 2020 Mar 14.

Department of Biochemistry, School of Medicine, Iran University of Medical Sciences, P.O. Box: 1449614535, Tehran, Iran.

Background: Pituitary adenomas as multifactorial intracranial neoplasms impose a massive burden of morbidity on patients and characterizing the molecular mechanism underlying their pathogenesis has received considerable attention. Despite the appealing role of cyclooxygenase enzymes and their bioactive lipid products in cancer pathogenesis, their relevance to pituitary adenoma pathogenesis is debated and yet to be determined. Thus, the current study perused this relevance.

Methods: The expression level of the isoforms of cyclooxygenase (COX-1 and COX-2) was evaluated in hormone-secreting and in-active pituitary adenoma tumors and normal pituitary tissues through Real-Time PCR. The level of PGE2, as the main product of enzymes, was assessed using enzyme immunoassay kits in patients and healthy subjects.

Results: The results of the current study demonstrated that COX-1 and COX-2 expression levels were increased in pituitary tumors including non-functional pituitary adenoma (NFPA), acromegaly, Cushing's disease and prolactinoma compared with normal pituitary tissues. A significant expression level of COX-2 was observed in NFPA compared with the other pituitary tumors. Furthermore, the COX-2 expression level was significantly increased in macroadenoma and invasive tumors. The level of PGE2 was consistent with COX enzymes enhanced in pituitary adenoma tumors compared with healthy pituitary tissue. A significant elevation in the PGE2 level was detected in NFPA compared with hormone-secreting pituitary tumors. Additionally, the PGE2 level was increased in macroadenoma compared with microadenoma and in invasive compared with non-invasive pituitary tumors. The diagnostic values of cyclooxygenase isoforms and PGE2 were considerable between patients and healthy groups; however, COX-2 revealed more value in distinguishing endocrinologically active and non-active pituitary tumors.

Conclusions: Data from the current study provides expression patterns of COX-1, COX-2 and PGE2 in prevalent pituitary tumors and their association with patients' clinical features which may open up new molecular targets for early diagnosis/follow up of pituitary tumor growth.
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http://dx.doi.org/10.1186/s12902-020-0515-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7071656PMC
March 2020

Respiratory syncytial virus infection: why does disease severity vary among individuals?

Expert Rev Respir Med 2020 04 3;14(4):415-423. Epub 2020 Feb 3.

Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

: Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory tract infections in infancy. While many infants are infected with RSV, the nature and severity of the disease vary among individuals. RSV causes bronchiolitis, pneumonia, and asthma exacerbation. However, most children infected with RSV have only mild upper airways disease and may be asymptomatic.: Despite efforts to elucidate mechanisms for the various clinical responses to RSV infection, they remain largely unknown, suggesting that susceptibility and disease are influenced by multiple intrinsic and extrinsic factors. This article reviews the available literature on the field of RSV disease severity and discusses important factors associated to susceptibility and different disease outcome.: The severity of RSV-induced illness is a phenomenon that depends on a variety of graded mechanisms of interaction between the host, virus, and environment. This may lead to differences in the intensity of immune response in the lung and different courses of the disease. By characterizing, classifying, and grading the affecting factors in high-risk patients versus those who do not fall ill by RSV, we may find therapies or point to disease-limiting medications.
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http://dx.doi.org/10.1080/17476348.2020.1724095DOI Listing
April 2020

Serum and tissue miRNAs: potential biomarkers for the diagnosis of cervical cancer.

Virol J 2019 10 7;16(1):116. Epub 2019 Oct 7.

Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, 1471613151, Iran.

Background: Finding new biomarkers for the early detection of cervical cancer is an essential requirement in this field. In this study, we aimed to evaluate the expression level of potential biomarkers in progression of cervical cancer in patients with cervical cancer compared to normal subjects.

Methods: The expression levels of tissue and serum miRNAs, including miR-9, miR-192 and miR-205, were investigated in 36 normal, 18 precancer, and 18 cervical cancer samples using real-time polymerase chain reaction.

Results: The results showed the higher significant expressions of miR-9, miR-192 and miR-205 in the tissue of cancer samples than those in the normal samples. Moreover, the miR-192 and miR-205 expression were significantly increased in the cancer group in comparison with the precancer group. Examination of serum samples revealed the increase in the expression level in the cancer groups than in the normal samples, for miR-9, miR-192 and miR-205 and the expressions of miR-9, miR-192 and miR-205 were significantly up-regulated in the precancer group in comparison with the normal group. Also the expression of miR-205 was remarkably increased in the cancer group in comparison with the precancer group. The receiver operating characteristic (ROC) analyses showed the highest area under the curve value for miR-192.

Conclusions: Given the increased expression level of miR-192 in cancer and in precancerous tissue and serum compared with the normal tissue and serum validated by analysing the ROC curve, miR-192 can be used as potential biomarker for the early detection of cervical cancer.
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http://dx.doi.org/10.1186/s12985-019-1220-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6781360PMC
October 2019

Up-regulation of 15-lipoxygenase enzymes and products in functional and non-functional pituitary adenomas.

Lipids Health Dis 2019 Jul 9;18(1):152. Epub 2019 Jul 9.

Department of Biochemistry, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Background: Pituitary adenoma accounts as a complex and multifactorial intracranial neoplasm with wide range of clinical symptoms which its underlying molecular mechanism has yet to be determined. The bioactive lipid mediators received attentions toward their contribution in cancer cell proliferation, progression and death. Amongst, 15-Lipoxygense (15-Lox) enzymes and products display appealing role in cancer pathogenesis which their possible effect in pituitary adenoma tumor genesis is perused in the current study.

Methods: The 15-Lipoxygenses isoforms expression level was evaluated in tumor tissues of prevalent functional and non-functional pituitary adenomas and normal pituitary tissues via Real-Time PCR. The circulating levels of 15(S) HETE and 13(S) HODE as 15-Lox main products were assessed in serum of patients and healthy subjects using enzyme immunoassay kits.

Results: Our results revealed that 15-Lox-1 and 15-Lox-2 expression levels were elevated in tumor tissues of pituitary adenomas comparing to normal pituitary tissues. The elevated levels of both isoforms were accompanied with 15(S) HETE and 13(S) HODE elevation in the serum of patients. The 15-Lox-1 expression and activity was higher in invasive tumors as well as tumors with bigger size indicating the possible pro-tumorigenic role of 15-Lox-1, more than 15-Lox-2 in pituitary adenomas. The diagnostic value of 15-Lipoxygense isoforms and products were considerable between patients and healthy groups.

Conclusion: The possible involvement of 15-Lipoxygense pathway especially 15-Lox-1 in the regulation of pituitary tumor growth and progression may open up new molecular mechanism regarding pituitary adenoma pathogenesis and might shed light on its new therapeutic strategies.
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http://dx.doi.org/10.1186/s12944-019-1089-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6617742PMC
July 2019

Molecular characterization of the glycoprotein and fusion protein in human respiratory syncytial virus subgroup A: Emergence of ON-1 genotype in Iran.

Infect Genet Evol 2019 07 1;71:166-178. Epub 2019 Apr 1.

Virology Department, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

HRSV is a principle cause of infant hospitalization, childhood wheezing and a common pathogen in the elderly. Limited information exists regarding HRSV genotypes in Iran. In order to better understand HRSV strain diversity, we performed an in-depth evaluation of the genetic variability of the HRSV F protein detected in children under two years of age that, presented with acute respiratory symptoms during 2015-2016 in Tehran. A total of 180 nasopharyngeal swabs were evaluated. The HRSV positive samples were genotyped for G and F gene sequences using RT-PCR and sequencing methods. Phylogenetic analysis was performed using the neighbor-joining and maximum likelihood methods. Genetic and antigenic characteristics of the F gene, nucleotide and amino acids in significant positions and immune system binding regions, as well as the p-distance, positive/negative selection site, linear epitopes and glycosylation sites were investigated in all selected sequences. Among the 83 HRSV positive samples, the Fifty-five cases were successfully sequenced. All of them were classified as subgroup A and belonged to the ON-1 genotype, which possessed 72-nt duplication in the G gene. This study is the first report on the emergence of ON-1 in Iran. ON-1 Iranian sequences clustered in three lineages according to virus fusion (F) gene variations. F gene sequence analysis showed that all genetic changes in the isolates from Iran were base substitutions and no deletion/insertions were identified. The low dN/dS ratio and lack of positively selected sites showed that the fusion genes found in the strains from Iran are not under host selective pressure. Continuing and long-term molecular epidemiological surveys for early detection of circulating and newly emerging genotypes are necessary to gain a better understanding of their epidemic potential.
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http://dx.doi.org/10.1016/j.meegid.2019.03.026DOI Listing
July 2019

Induction of protective immune response to intranasal administration of influenza virus-like particles in a mouse model.

J Cell Physiol 2019 Feb 19. Epub 2019 Feb 19.

Virology Department, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Human influenza A viruses (IAVs) cause global pandemics and epidemics, which remains a nonignorable serious concern for public health worldwide. To combat the surge of viral outbreaks, new treatments are urgently needed. Here, we design a new vaccine based on virus-like particles (VLPs) and show how intranasal administration of this vaccine triggers protective immunity, which can be exploited for the development of new therapies. H1N1 VLPs were produced in baculovirus vectors and were injected into BALB/c mice by the intramuscular (IM) or intranasal (IN) route. We found that there were significantly higher inflammatory cell and lymphocyte concentrations in bronchoalveolar lavage samples and the lungs of IN immunized mice; however, the IM group had little signs of inflammatory responses. On the basis of our results, immunization with H1N1 influenza VLP elicited a strong T cell immunity in BALB/c mice. Despite T cell immunity amplification after both IN and IM vaccination methods in mice, IN-induced T cell responses were significantly more intense than IM-induced responses, and this was likely related to an increased number of both CD11b and CD103 dendritic cells in mice lungs after IN administration of VLP. Furthermore, evaluation of interleukin-4 and interferon gamma cytokines along with several chemokine receptors showed that VLP vaccination via IN and IM routes leads to a greater CD4 Th1 and Th2 response, respectively. Our findings indicated that VLPs represent a potential strategy for the development of an effective influenza vaccine; however, employing relevant routes for vaccination can be another important part of the universal influenza vaccine puzzle.
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http://dx.doi.org/10.1002/jcp.28339DOI Listing
February 2019

The interplay between vitamin D and viral infections.

Rev Med Virol 2019 03 6;29(2):e2032. Epub 2019 Jan 6.

Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

The pleiotropic role of vitamin D has been explored over the past decades and there is compelling evidence for an epidemiological association between poor vitamin D status and a variety of diseases. While the potential anti-viral effect of vitamin D has recently been described, the underlying mechanisms by which vitamin D deficiency could contribute to viral disease development remain poorly understood. The possible interactions between viral infections and vitamin D appear to be more complex than previously thought. Recent findings indicate a complex interplay between viral infections and vitamin D, including the induction of anti-viral state, functional immunoregulatory features, interaction with cellular and viral factors, induction of autophagy and apoptosis, and genetic and epigenetic alterations. While crosstalk between vitamin D and intracellular signalling pathways may provide an essential modulatory effect on viral gene transcription, the immunomodulatory effect of vitamin D on viral infections appears to be transient. The interplay between viral infections and vitamin D remains an intriguing concept, and the global imprint that vitamin D can have on the immune signature in the context of viral infections is an area of growing interest.
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http://dx.doi.org/10.1002/rmv.2032DOI Listing
March 2019

Disease severity in respiratory syncytial virus infection: Role of host genetic variation.

Rev Med Virol 2019 03 4;29(2):e2026. Epub 2019 Jan 4.

Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Respiratory syncytial virus (RSV) infection is the most common cause of bronchiolitis and pneumonia in the pediatric population worldwide. The immunopathology of RSV infection varies considerably and severe disease occurs only in a minority of the population. There are many factors (host, viral, and environmental) that contribute to the complicated disease phenotype. In this regard, host factors are decisive for pulmonary susceptibility to RSV infection. Host genetic diversity certainly affects the balance between control of viral replication and tissue damage during RSV infection, consequently impacting on diseases outcome. In this review, we discuss the role of host genetic variation in disease caused by RSV aiming to highlight genetic risk factors for one of the most common diseases in early childhood. Our findings clearly indicate that the response of each individual to infection is influenced by genetic diversity mainly linked to the regulation of host immune responses. Future genetic association and functional studies using more powerful and consistently reproducible approaches will likely be able to confirm, refine, and expand our developing concept of RSV disease pathogenesis.
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http://dx.doi.org/10.1002/rmv.2026DOI Listing
March 2019

The role of expression and activity of 15-Lipoxygenase isoforms and related cytokines in patients with Multiple Sclerosis and healthy controls.

J Neuroimmunol 2018 12 18;325:32-42. Epub 2018 Oct 18.

Department of Biochemistry, School of Medicine, Iran University of Medical Sciences, Tehran, Iran. Electronic address:

Background: Multiple Sclerosis (MS) as an inflammatory multifactorial auto immune nervous system disease imposes devastating burden of morbidity worldwide. Among environmental and genetic factors, the relevance of inflammatory mediators in MS pathogenesis is well documented. 15-Lipoxygense enzyme and its derived products have received attention as possible mediators of inflammatory responses. The involvement of 15-Lipoxygense pathway in the pathogenesis of inflammatory diseases such as MS has yet to be illustrated which is perused in the current study.

Methods: The expression level of 15-Lipoxygense isoforms was assessed via Real-Time PCR in the peripheral blood mononuclear cells separated from patients with MS and healthy subjects. The level of 15-Lipoxygense products (15(S) HETE, 13(S) HODE) and related cytokines (IL4 and IL13) were evaluated using enzyme immunoassay kits in serum samples.

Results: Our results demonstrated that 15-Lipoxygense-1 and 15-Lipoxygense-2 expression levels were increased in patients suffering from MS comparing to healthy subjects which were more obvious in Relapsing-Remitting MS. The elevated levels of 15-Lipoxygense isoforms were accompanied with 15(S) HETE and 13(S) HODE enhancement in serum of patients and the IL 13 elevation but not IL4 was consistent with higher expression of 15-Lipoxygense. The diagnostic value of 15-Lipoxygense isoforms and products were considerable between patients and healthy groups.

Conclusion: The possible effect of 15-Lipoxygense pathway in the regulation of inflammatory events may light up new therapeutic possibilities regarding MS pathogenesis.
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http://dx.doi.org/10.1016/j.jneuroim.2018.10.009DOI Listing
December 2018

Correction to: Blocking of opioid receptors in experimental formaline-inactivated respiratory syncytial virus (FI-RSV) immunopathogenesis: from beneficial to harmful impacts.

Med Microbiol Immunol 2018 11;207(5-6):345

Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

In the original publication, seventh author's name was incorrectly published as 'Maryam Golaram'.
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http://dx.doi.org/10.1007/s00430-018-0562-1DOI Listing
November 2018

Anti-Inflammatory MicroRNAs and Their Potential for Inflammatory Diseases Treatment.

Front Immunol 2018 25;9:1377. Epub 2018 Jun 25.

Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Inflammation is a complicated biological and pathophysiological cascade of responses to infections and injuries, and inflammatory mechanisms are closely related to many diseases. The magnitude, the complicated network of pro- and anti-inflammatory factors, and the direction of the inflammatory response can impact on the development and progression of various disorders. The currently available treatment strategies often target the symptoms and not the causes of inflammatory disease and may often be ineffective. Since the onset and termination of inflammation are crucial to prevent tissue damage, a range of mechanisms has evolved in nature to regulate the process including negative and positive feedback loops. In this regard, microRNAs (miRNAs) have emerged as key gene regulators to control inflammation, and it is speculated that they are fine-tune signaling regulators to allow for proper resolution and prevent uncontrolled progress of inflammatory reactions. In this review, we discuss recent findings related to significant roles of miRNAs in immune regulation, especially the potential utility of these molecules as novel anti-inflammatory agents to treat inflammatory diseases. Furthermore, we discuss the possibilities of using miRNAs as drugs in the form of miRNA mimics or miRNA antagonists.
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http://dx.doi.org/10.3389/fimmu.2018.01377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6026627PMC
June 2018

Investigation of the Cellular Immune Response to Recombinant Fragments of Filamentous Hemagglutinin and Pertactin of Bordetella pertussis in BALB/c Mice.

J Interferon Cytokine Res 2018 04;38(4):161-170

1 Department of Immunology, Tehran University of Medical Sciences , Tehran, Iran .

Vaccination with whole-cell or acellular (Ac) vaccines has been very effective for the control of pertussis. The immune response to Ac vaccines has been generally associated with a shift toward the Th2 profile. In the present study, overlapping recombinant fragments of filamentous hemagglutinin (FHA) and pertactin (PRN) were produced in Escherichia coli. BALB/c mice were immunized with recombinant FHA and PRN together with the native pertussis toxin and alum or CpG as adjuvant. Immunized mice were subsequently aerosol challenged with Bordetella pertussis. Bacterial growth was assessed in bronchoalveolar lavage samples and the levels of cytokines were quantitated in supernatants of stimulated splenocytes by enzyme-linked immunosorbent assay. Our results demonstrated that both PRN and FHA antigens were able to induce IFN-γ, IL-4, and to some extent IL-17 cytokines in challenged mice. The level of IFN-γ was higher in response to CpG formulated antigens. These findings indicate immunoprotective efficacy of our recombinant FHA and PRN antigens in mice.
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http://dx.doi.org/10.1089/jir.2017.0060DOI Listing
April 2018

No genetic association between A118G polymorphism of μ-opioid receptor gene and schizophrenia and bipolar disorders.

Indian J Psychiatry 2017 Oct-Dec;59(4):483-486

Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Background: Schizophrenia (SZ) and bipolar disorder (BD) are chronic and multifactorial psychiatric disorders that might be affected by different genes in combination with environmental factors. There is evidence of association between polymorphisms of μ-opioid receptor gene (OPRM1) with these disorders.

Objectives: The aim of this study was to investigate the genetic association between OPRM1 A118G SNP in SZ and BD patients in comparison with healthy controls (HCs).

Materials And Methods: One single-nucleotide polymorphism in OPRM1 was genotyped using TaqMan real-time PCR assay in 203 SZ and BD patients and 389 HCs.

Results: There was no statistically significant difference in genotypic and allelic frequencies of OPRM1 A118G SNP between HCs and SZ/BD patients.

Conclusions: To find the underlying genetic factors associated with these complex disorders, further studies need to be conducted using larger sample size, different genetic populations, and different gene variations.
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http://dx.doi.org/10.4103/psychiatry.IndianJPsychiatry_53_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5806329PMC
March 2018

The Role of Cannabinoid Receptor 1 in the Immunopathology of Respiratory Syncytial Virus.

Viral Immunol 2018 05 20;31(4):292-298. Epub 2018 Feb 20.

1 Department of Virology, School of Public Health, Tehran University of Medical Sciences , Tehran, Iran .

Endocannabinoid system plays an important role in pathophysiologic processes such as immune functions and impacts on disease severity. Our previous study showed that cannabinoid receptor 2 (CB2) affects clinical course of respiratory syncytial virus (RSV) infection. In this study, we investigated the role of cannabinoid receptor 1 (CB1) in RSV immunopathology and its therapeutic potential in mice model. To study the role of CB1 receptors in the immunopathology of RSV, CB1 was blocked daily with AM281 as a selective antagonist in Balb/c mice and were infected by intranasal inoculation of RSV-A2 24 h following the first dose of antagonist administration. The potential pharmacological therapeutic effects of cannabinoid receptor activation during RSV infection were studied using JZL184 as a selective indirect agonist, 24 h after infection. Mice were sacrificed on day 5 after infection and experimental analyses were performed to study the CB1 receptor expression, airway immune cell influx, cytokine/chemokine secretion, lung histopathology, and viral load. RSV infection of airways significantly induced the expression of CB1 receptors in lung cells of mice. Blockade of CB1 receptors using AM281 enhanced immune cell influx and cytokine/chemokine production, and aggravated lung pathology. Activation of cannabinoid receptors using JZL184 decreased immune cell influx and cytokine/chemokine production, and alleviated lung pathology. This study and our previous finding indicated that endocannabinoid signaling regulates the inflammatory response to RSV infection, and is a potential therapeutic candidate for alleviation of RSV-associated immunopathology.
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http://dx.doi.org/10.1089/vim.2017.0098DOI Listing
May 2018

Blocking of opioid receptors in experimental formaline-inactivated respiratory syncytial virus (FI-RSV) immunopathogenesis: from beneficial to harmful impacts.

Med Microbiol Immunol 2018 04 18;207(2):105-115. Epub 2017 Dec 18.

Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Opioid system plays a significant role in pathophysiological processes, such as immune response and impacts on disease severity. Here, we investigated the effect of opioid system on the immunopathogenesis of respiratory syncytial virus (RSV) vaccine (FI-RSV)-mediated illness in a widely used mouse model. Female Balb/c mice were immunized at days 0 and 21 with FI-RSV (2 × 10 pfu, i.m.) and challenged with RSV-A2 (3 × 10 pfu, i.n.) at day 42. Nalmefene as a universal opioid receptors blocker administered at a dose of 1 mg/kg in combination with FI-RSV (FI-RSV + NL), and daily after live virus challenge (RSV + NL). Mice were sacrificed at day 5 after challenge and bronchoalveolar lavage (BAL) fluid and lungs were harvested to measure airway immune cells influx, T lymphocyte subtypes, cytokines/chemokines secretion, lung histopathology, and viral load. Administration of nalmefene in combination with FI-RSV (FI-RSV + NL-RSV) resulted in the reduction of the immune cells infiltration to the BAL fluid, the ratio of CD4/CD8 T lymphocyte, the level of IL-5, IL-10, MIP-1α, lung pathology, and restored weight loss after RSV infection. Blocking of opioid receptors during RSV infection in vaccinated mice (FI-RSV-RSV + NL) had no significant effects on RSV immunopathogenesis. Moreover, administration of nalmefene in combination with FI-RSV and blocking opioid receptors during RSV infection (FI-RSV + NL-RSV + NL) resulted in an increased influx of the immune cells to the BAL fluid, increases the level of IFN-γ, lung pathology, and weight loss in compared to control condition. Although nalmefene administration within FI-RSV vaccine decreases vaccine-enhanced infection during subsequent exposure to the virus, opioid receptor blocking during RSV infection aggravates the host inflammatory response to RSV infection. Thus, caution is required due to beneficial/harmful functions of opioid systems while targeting as potentially therapies.
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http://dx.doi.org/10.1007/s00430-017-0531-0DOI Listing
April 2018

Sodium butyrate promotes apoptosis in breast cancer cells through reactive oxygen species (ROS) formation and mitochondrial impairment.

Lipids Health Dis 2017 Nov 2;16(1):208. Epub 2017 Nov 2.

Department of Biochemistry, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Background: Sodium butyrate (NaBu) is a short-chain fatty acid which serves as a histon deacetylase inhibitor and has received considerable interest as a possible regulator of cancer cell death. The regulatory effect of NaBu on cancer cell growth or death has yet to be illustrated in many cancers including breast cancer. This study is aimed to elucidate the possible effect of NaBu on regulation of breast cancer growth and apoptosis.

Methods: The cytotoxic effect of NaBu on the growth of breast cancer cells (MCF-7 and MDA-MB-468) and normal breast cells (MCF-10A) was determined using MTT assay. Annexin-V-FITC staining and PI staining were performed to detect apoptosis and cell cycle distribution using Flow cytometry, the level of mitochondrial membrane potential (Δψm), Reactive oxygen species (ROS)formation and caspase activity were determined accordingly.

Results: Based on our data, NaBu induced a dose and time-dependent cell toxicity in breast cancer cells which was related to the cell cycle arrest and induction of apoptosis. The impact of NaBu on MCF-10A cell toxicity, cell cycle distribution and apoptosis was inconsiderable. NaBu-elicited apoptosis was accompanied by the elevated level of ROS, increased caspase activity and reduced mitochondrial membrane potential (Δψm) in MCF-7 and MDA-MB-468 cells and with no effect on the above mentioned factors in MCF-10A cells.

Conclusions: Our study provided insight in to the role of NaBu on the regulation of breast cancer cell growth and lighten up the pro-apoptotic activity of NaBu.
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http://dx.doi.org/10.1186/s12944-017-0593-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5669027PMC
November 2017

Effects of cannabinoid receptor type 2 in respiratory syncytial virus infection in human subjects and mice.

Virulence 2018 01 8;9(1):217-230. Epub 2017 Dec 8.

a Department of Virology , School of Public Health, Tehran University of Medical Sciences , Tehran , Iran.

An accumulating body of evidence suggests that the endocannabinoid system plays a significant role in pathophysiological processes and impacts disease severity. Here we investigate the possible role of a cannabinoid receptor type 2 (CB2) functional variant in determining disease severity and the potential pharmacological therapeutic effects of CB2 activation in viral respiratory infection. The common missense variant (CAA/CGG; Q63R) of the gene-encoding CB2 receptor (CNR2) was evaluated in 90 inpatient and 90 outpatient children with acute respiratory tract infection (ARTI). The frequency distribution of respiratory syncytial virus (RSV)-the main cause of severe cases of bronchiolitis and pneumonia in children-was studied in all collected samples. The mechanism through which CB2 affects clinical outcomes in case of RSV infection was studied in Balb/c mice model using AM630 as a CB2 antagonist. The potential therapeutic effect of CB2 activation during RSV infection was studied using a selective agonist, JWH133. The CB2 Q63R variation was associated with increased risk of hospitalization in children with ARTI. Children carrying the QQ genotype were more prone to developing severe ARTI (OR = 3.275, 95% CI: 1.221-8.705; p = 0.019). Of all the children enrolled in the study, 83 patients (46.1%) were found positive for RSV infection. The associated risk of developing severe ARTI following RSV infection increased more than two-fold in children carrying the Q allele (OR = 2.148, 95% CI: 1.092-4.224; p = 0.026). In mice, the blockade of CB2 by AM630 during RSV infection enhanced the influx of BAL cells and production of cytokines/chemokines while exaggerating lung pathology. CB2 activation by JWH133 reduces the influx of BAL cells and production of cytokines/chemokines while alleviating lung pathology. Collectively, CB2 is associated with RSV severity during infancy and may serve as a therapeutic target in RSV infection through the alleviation of virus-associated immunopathology.
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http://dx.doi.org/10.1080/21505594.2017.1389369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5955186PMC
January 2018

Targeting human breast cancer cells by an oncolytic adenovirus using microRNA-targeting strategy.

Virus Res 2017 08 1;240:207-214. Epub 2017 Sep 1.

Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, 1471613151, Iran. Electronic address:

MicroRNA-targeting strategy is a promising approach that enables oncolytic viruses to replicate in tumor cells but not in normal cells. In this study, we targeted adenoviral replication toward breast cancer cells by inserting ten complementary binding sites for miR-145-5p downstream of E1A gene. In addition, we evaluated the effect of increasing miR-145 binding sites on inhibition of virus replication. Ad5-control and adenoviruses carrying five or ten copies of miR145-5p target sites (Ad5-5miR145T, Ad5-10miR145T) were generated and inoculated into MDA-MB-453, BT-20, MCF-7 breast cancer cell lines and human mammary epithelial cells (HMEpC). Titer of Ad5-10miR145T in HMEpC was significantly lower than Ad5-control titer. Difference between the titer of these two viruses at 12, 24, 36, and 48h after infection was 1.25, 2.96, 3.06, and 3.77 log TCID. No significant difference was observed between the titer of both adenoviruses in MDA-MB-453, BT-20 and MCF-7 cells. The infectious titer of adenovirus containing 10 miR-145 binding sites in HMEpC cells at 24, 36, and 48h post-infection was 1.7, 2.08, and 4-fold, respectively, lower than the titer of adenovirus carrying 5 miR-145 targets. Our results suggest that miR-145-targeting strategy provides selectivity for adenovirus replication in breast cancer cells. Increasing the number of miRNA binding sites within the adenoviral genome confers more selectivity for viral replication in cancer cells.
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http://dx.doi.org/10.1016/j.virusres.2017.08.016DOI Listing
August 2017

Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015: a systematic review and modelling study.

Authors:
Ting Shi David A McAllister Katherine L O'Brien Eric A F Simoes Shabir A Madhi Bradford D Gessner Fernando P Polack Evelyn Balsells Sozinho Acacio Claudia Aguayo Issifou Alassani Asad Ali Martin Antonio Shally Awasthi Juliet O Awori Eduardo Azziz-Baumgartner Henry C Baggett Vicky L Baillie Angel Balmaseda Alfredo Barahona Sudha Basnet Quique Bassat Wilma Basualdo Godfrey Bigogo Louis Bont Robert F Breiman W Abdullah Brooks Shobha Broor Nigel Bruce Dana Bruden Philippe Buchy Stuart Campbell Phyllis Carosone-Link Mandeep Chadha James Chipeta Monidarin Chou Wilfrido Clara Cheryl Cohen Elizabeth de Cuellar Duc-Anh Dang Budragchaagiin Dash-Yandag Maria Deloria-Knoll Mukesh Dherani Tekchheng Eap Bernard E Ebruke Marcela Echavarria Carla Cecília de Freitas Lázaro Emediato Rodrigo A Fasce Daniel R Feikin Luzhao Feng Angela Gentile Aubree Gordon Doli Goswami Sophie Goyet Michelle Groome Natasha Halasa Siddhivinayak Hirve Nusrat Homaira Stephen R C Howie Jorge Jara Imane Jroundi Cissy B Kartasasmita Najwa Khuri-Bulos Karen L Kotloff Anand Krishnan Romina Libster Olga Lopez Marilla G Lucero Florencia Lucion Socorro P Lupisan Debora N Marcone John P McCracken Mario Mejia Jennifer C Moisi Joel M Montgomery David P Moore Cinta Moraleda Jocelyn Moyes Patrick Munywoki Kuswandewi Mutyara Mark P Nicol D James Nokes Pagbajabyn Nymadawa Maria Tereza da Costa Oliveira Histoshi Oshitani Nitin Pandey Gláucia Paranhos-Baccalà Lia N Phillips Valentina Sanchez Picot Mustafizur Rahman Mala Rakoto-Andrianarivelo Zeba A Rasmussen Barbara A Rath Annick Robinson Candice Romero Graciela Russomando Vahid Salimi Pongpun Sawatwong Nienke Scheltema Brunhilde Schweiger J Anthony G Scott Phil Seidenberg Kunling Shen Rosalyn Singleton Viviana Sotomayor Tor A Strand Agustinus Sutanto Mariam Sylla Milagritos D Tapia Somsak Thamthitiwat Elizabeth D Thomas Rafal Tokarz Claudia Turner Marietjie Venter Sunthareeya Waicharoen Jianwei Wang Wanitda Watthanaworawit Lay-Myint Yoshida Hongjie Yu Heather J Zar Harry Campbell Harish Nair

Lancet 2017 Sep 7;390(10098):946-958. Epub 2017 Jul 7.

Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland, UK; Public Health Foundation of India, New Delhi, India. Electronic address:

Background: We have previously estimated that respiratory syncytial virus (RSV) was associated with 22% of all episodes of (severe) acute lower respiratory infection (ALRI) resulting in 55 000 to 199 000 deaths in children younger than 5 years in 2005. In the past 5 years, major research activity on RSV has yielded substantial new data from developing countries. With a considerably expanded dataset from a large international collaboration, we aimed to estimate the global incidence, hospital admission rate, and mortality from RSV-ALRI episodes in young children in 2015.

Methods: We estimated the incidence and hospital admission rate of RSV-associated ALRI (RSV-ALRI) in children younger than 5 years stratified by age and World Bank income regions from a systematic review of studies published between Jan 1, 1995, and Dec 31, 2016, and unpublished data from 76 high quality population-based studies. We estimated the RSV-ALRI incidence for 132 developing countries using a risk factor-based model and 2015 population estimates. We estimated the in-hospital RSV-ALRI mortality by combining in-hospital case fatality ratios with hospital admission estimates from hospital-based (published and unpublished) studies. We also estimated overall RSV-ALRI mortality by identifying studies reporting monthly data for ALRI mortality in the community and RSV activity.

Findings: We estimated that globally in 2015, 33·1 million (uncertainty range [UR] 21·6-50·3) episodes of RSV-ALRI, resulted in about 3·2 million (2·7-3·8) hospital admissions, and 59 600 (48 000-74 500) in-hospital deaths in children younger than 5 years. In children younger than 6 months, 1·4 million (UR 1·2-1·7) hospital admissions, and 27 300 (UR 20 700-36 200) in-hospital deaths were due to RSV-ALRI. We also estimated that the overall RSV-ALRI mortality could be as high as 118 200 (UR 94 600-149 400). Incidence and mortality varied substantially from year to year in any given population.

Interpretation: Globally, RSV is a common cause of childhood ALRI and a major cause of hospital admissions in young children, resulting in a substantial burden on health-care services. About 45% of hospital admissions and in-hospital deaths due to RSV-ALRI occur in children younger than 6 months. An effective maternal RSV vaccine or monoclonal antibody could have a substantial effect on disease burden in this age group.

Funding: The Bill & Melinda Gates Foundation.
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http://dx.doi.org/10.1016/S0140-6736(17)30938-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5592248PMC
September 2017

Molecular Epidemiology of Human Respiratory Syncytial Virus in Iranian ≥60 Years Old Hospitalized Patients with Acute Respiratory Symptoms.

Arch Iran Med 2017 Jun;20(6):368-375

Department of Virology - School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Background: Human respiratory syncytial virus (HRSV) is an important cause of acute respiratory infection (ARI) and mortality in ≥60 years old population around the world. The aim of this study was to determine the frequency and circulating genotypes of HRSV in Iranian patients ≥ 60 years old.

Methods: In this cross-sectional molecular epidemiology study, we examined the C-terminal located hypervariable domain of G glycoprotein of HRSV in throat swabs from Tehran, Hormozgan, Boushehr, West Azarbayjan, Ghom and Alborz provinces of Iran which were addressed to national influenza center between October 2013 and March 2015. During these two consecutive years, a total of 225 samples collected from patients older than 60 years were tested using RT hemi-nested PCR and sequencing and the acquired sequences were phylogenetically analyzed.

Results: Sixteen out of 225 samples (7.1%) yielded a positive result. Among the positive samples, 13 cases (81%) pertained to antigenic group A and the remaining 3 cases (19%) belonged to group B. Three genotypes including GA1, GA2 and BA9 were identified in the first year of survey whereas during the second year, only GA1 and GA2 genotypes were detected.

Conclusion: Our study indicates that HRSV genotypes from both A and B antigenic groups which were discovered in pediatric population previously, are circulating among Iranian ≥60 years old population.
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http://dx.doi.org/0172006/AIM.009DOI Listing
June 2017