Publications by authors named "Maryam Esghaei"

58 Publications

Liver Function Tests Profile in COVID-19 Patients at the Admission Time: A Systematic Review of Literature and Conducted Researches.

Adv Biomed Res 2020 23;9:74. Epub 2020 Dec 23.

Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran.

Background: Since the start of coronavirus epidemic in Wuhan, China, in early December 2019, many literatures addressed its epidemiology, virology, and clinical presentation. In this review, we systematically reviewed the published literature in the field of liver function tests profile in COVID-19 patients at the admission time.

Materials And Methods: systematic literature search were performed in EMBASE, PubMed, Science Direct, and Scopus using "severe acute respiratory syndrome 2 coronavirus (SARS-CoV-2)", "SARS," "SARS-CoV," "coronavirus," "novel coronavirus," "liver," "hepatitis," "Liver function" keywords. The search was limited to range from 2019 to May 19, 2020.

Results: From a total 7298 articles, 145 were screened and 18 were eligible for further analysis. The highest rate of liver associated comorbidities was reported 11%. The aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were the most frequent assessed enzymes. Increase in AST level was seen in 10%-53% of patients while The ALT increase was seen in 5%-28% of COVID-19 patients at the admission time. The prothrombin time was increase in 7%-12% of patients and the D-dimer was reports increase in 14%-36% of COVID-19 patients at the admission time. Furthermore, albumin decrease was seen in 6%-98% of COVID-19 patients at the admission time.

Conclusion: In conclusion, by using the results of study, it could be suggested that the liver function tests assessment is critical assessment in COVID-19 patients at the admission time. This liver function test could be used as potential prognostic factor in COVID-19 severity in future.
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http://dx.doi.org/10.4103/abr.abr_73_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059456PMC
December 2020

The role of telomerase and viruses interaction in cancer development, and telomerase-dependent therapeutic approaches.

Cancer Treat Res Commun 2021 Jan 27;27:100323. Epub 2021 Jan 27.

Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, Iran. Electronic address:

Human telomerase reverse transcriptase (hTERT) is an enzyme that is critically involved in elongating and maintaining telomeres length to control cell life span and replicative potential. Telomerase activity is continuously expressed in human germ-line cells and most cancer cells, whereas it is suppressed in most somatic cells. In normal cells, by reducing telomerase activity and progressively shortening the telomeres, the cells progress to the senescence or apoptosis process. However, in cancer cells, telomere lengths remain constant due to telomerase's reactivation, and cells continue to proliferate and inhibit apoptosis, and ultimately lead to cancer development and human death due to metastasis. Studies demonstrated that several DNA and RNA oncoviruses could interact with telomerase by integrating their genome sequence within the host cell telomeres specifically. Through the activation of the hTERT promoter and lengthening the telomere, these cells contributes to cancer development. Since oncoviruses can activate telomerase and increase hTERT expression, there are several therapeutic strategies based on targeting the telomerase of cancer cells like telomerase-targeted peptide vaccines, hTERT-targeting dendritic cells (DCs), hTERT-targeting gene therapy, and hTERT-targeting CRISPR/Cas9 system that can overcome tumor-mediated toleration mechanisms and specifically apoptosis in cancer cells. This study reviews available data on the molecular structure of telomerase and the role of oncoviruses and telomerase interaction in cancer development and telomerase-dependent therapeutic approaches to conquest the cancer cells.
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http://dx.doi.org/10.1016/j.ctarc.2021.100323DOI Listing
January 2021

As Evidence-Based Tumorigenic Role of Epstein-Barr Virus miR-BART1-3p in Neurological Tumors.

Asian Pac J Cancer Prev 2021 Jan 1;22(1):257-266. Epub 2021 Jan 1.

Department of Virology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Introduction: Central nervous system tumors are a diverse group of tumors that account for 2% of all adult cancers and 17% of childhood malignancies. Several internal and external risk factors are involved in the development of this cancer such as viral infections. The aim of this study was to the determination of the EBV infection frequency and the expression level of miR-122 and miR-BART in CNS tumors samples.

Methods: One hundred and thirty-eight  fresh tissue sample (106 case and 32 control) was collected from CNS specimens. The presence of Epstein-Barr virus (EBV) DNA was examined by PCR assay and the expression level of miR-122 and miR-BART were evaluated by using real-time PCR assay in CNS tissue samples.

Results: EBV DNA was detected in 17% (18 of 106) of tumors tissue samples and 6.4% (2 of 32) of control samples. according to results, there was a significant relationship between the presence of EBV-DNA with CNS tumors. Additionally, the expression level of miR-122 was significantly downregulated in the EBV-positive sample compared to that of the EBV-negative sample. Also, the level of EBV-BART1-3p expression was significantly higher in EBV-positive tumors samples than EBV-positive normal samples.

Conclusion: The results of this study suggest that the EBV could change the condition of cancer cells by altering the expression of miR-122 and EBV-BART1-3p and maybe contribute to the development of cancer cells. However, the role of viral infections in CNS cancer requires further studies. 
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http://dx.doi.org/10.31557/APJCP.2021.22.1.257DOI Listing
January 2021

Evolutionary study of COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as an emerging coronavirus: Phylogenetic analysis and literature review.

Vet Med Sci 2021 03 18;7(2):559-571. Epub 2020 Nov 18.

Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran.

Since emerging coronaviruses have always become a human health concern globally especially severe acute respiratory syndrome coronavirus 2 (SARS-CoV) and Middle East respiratory syndrome coronavirus and a novel coronavirus was introduced in Wuhan, China, in December 2019 (called SARS-CoV-2), many researchers focused on its epidemics, virological and clinical features. SARS-CoV-2 is classified as Betacoronaviruses genus and Sarbecovirus subgenus (lineage B). The virus shows a great similarity with SARS-CoV and bat SARS-like coronaviruses. In this study, we evaluate SARS-CoV-2 virus phylogeny and evolution by using current virus and related sequences.
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http://dx.doi.org/10.1002/vms3.394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753621PMC
March 2021

Signal transduction pathway mutations in gastrointestinal (GI) cancers: a systematic review and meta-analysis.

Sci Rep 2020 10 30;10(1):18713. Epub 2020 Oct 30.

Gastrointestinal and Liver Disease Research Center, Iran University of Medical Sciences, Tehran, Iran.

The present study was conducted to evaluate the prevalence of the signaling pathways mutation rate in the Gastrointestinal (GI) tract cancers in a systematic review and meta-analysis study. The study was performed based on the PRISMA criteria. Random models by confidence interval (CI: 95%) were used to calculate the pooled estimate of prevalence via Metaprop command. The pooled prevalence indices of signal transduction pathway mutations in gastric cancer, liver cancer, colorectal cancer, and pancreatic cancer were 5% (95% CI: 3-8%), 12% (95% CI: 8-18%), 17% (95% CI: 14-20%), and 20% (95% CI: 5-41%), respectively. Also, the mutation rates for Wnt pathway and MAPK pathway were calculated to be 23% (95% CI, 14-33%) and 20% (95% CI, 17-24%), respectively. Moreover, the most popular genes were APC (in Wnt pathway), KRAS (in MAPK pathway) and PIK3CA (in PI3K pathway) in the colorectal cancer, pancreatic cancer, and gastric cancer while they were beta-catenin and CTNNB1 in liver cancer. The most altered pathway was Wnt pathway followed by the MAPK pathway. In addition, pancreatic cancer was found to be higher under the pressure of mutation compared with others based on pooled prevalence analysis. Finally, APC mutations in colorectal cancer, KRAS in gastric cancer, and pancreatic cancer were mostly associated gene alterations.
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http://dx.doi.org/10.1038/s41598-020-73770-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7599243PMC
October 2020

The First Detection of Co-Infection of Double-Stranded RNA Virus 1, 2 and 3 in Iranian Isolates of .

Iran J Parasitol 2020 Jul-Sep;15(3):357-363

Student Research Committee, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Background: The Totiviridae family includes a number of double-stranded RNA viruses that can infect . Some isolates are infected with one or more double-stranded RNA (dsRNA) viruses. In this study, different strains of double-stranded RNA virus in Iranian isolates of were evaluated for the first time in Iran.

Methods: Vaginal swabs were collected from 1550 participants who were referred to hospitals associated with Iran University of Medical Sciences, Tehran, Iran from June to November 2018. isolates were cultured in Diamond's modified medium. After the extraction of nucleic acids using a DNA/RNA extraction kit, RT-PCR was performed and PCR products were purified and sequenced.

Results: In general 9 (0.6%) isolates were confirmed as among 1550 collected vaginal samples. Among 9 isolates of , three of them were infected with TVV1. One isolate has multiple infections with virus (TVV1, TVV2 and TVV3) as coinfection. The nucleotide BLAST indicated that the virus 1(TVV1) isolates were most closely related to TVV1-OC5, TVV1-UR1-1.The virus 2 (TVV2) sequence had also a similarity with TVV2-UR1-1, TVV2-UR1 and TVV2-OC3. The sequence of virus 3(TVV3) had similarity with TVV3-OC5, TVV3-UR1-1 and TVV3-UR1.

Conclusion: Three dsRNA viruses virus (TVV1, TVV2 and TVV3) were detected using RT-PCR in Iranian isolates. The coinfection of TVV1, TVV2 and TVV3 in one isolate of was observed for the first time in Iran.
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http://dx.doi.org/10.18502/ijpa.v15i3.4200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7548462PMC
October 2020

The effect of improved formulation of chitosan-alginate microcapsules of Bifidobacteria on serum lipid profiles in mice.

Microb Pathog 2020 Dec 17;149:104585. Epub 2020 Oct 17.

Department of Microbiology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran; Microbial Biotechnology Research Center, Iran University of Medical Sciences, Tehran, Iran. Electronic address:

Background: Probiotics have been associated with many beneficial effects in human digestive physiology. The aim of this study was to evaluate the effect of improved formulation of chitosan-alginate microcapsules of Bifidobacterium strains on serum triglycerides, cholesterol, HDL, and LDL in mice.

Methods: Five approved probiotic strains of Bifidobacterium were tested for anti-proliferative effect and interleukin-8 induction on HT-29 cell lines. Bifidobacterium strains plus five approved Lactobacillus were encapsulated in chitosan-alginate microcapsules and tested for its survival in simulated gastrointestinal conditions. These microcapsules were administered to 4 groups of mice (including 1. Bif (Bifidobacterium strains), 2. Lac (Lactobacillus strains), 3. Bif-Lac (Bifidobacterium plus Lactobacillus strains) and 4. Control) for 8 days. At eighth day, the blood of mice were taken and serum levels of triglycerides, cholesterol, HDL, and LDL of them were determined.

Results: All of the Bifidobacterium strains significantly (P < 0.001) reduced secretion of IL-8 in HT-29 cells as well as maximum antiproliferative effects (P < 0.001). In addition, all microcapsules showed impressive survival rate in bile (>%94.1) and gastrointestinal (>%78.28) conditions (P < 0.05). Only Bif-Lac group displayed significantly lower serum cholesterol and LDL levels than control group (P < 0.05). Besides, all groups indicate statistically significant weight loss of mice during the 8 days in comparison with the control group (P < 0.05).

Conclusion: The results of this study showed that the microencapsulated probiotics with alginate and chitosan had an effective mean of delivery of viable bacterial cells and non-pharmacological interventions use to reduce serum cholesterol and LDL levels in in-vivo condition.
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http://dx.doi.org/10.1016/j.micpath.2020.104585DOI Listing
December 2020

The assessment of a possible link between HPV-mediated inflammation, apoptosis, and angiogenesis in Prostate cancer.

Int Immunopharmacol 2020 Nov 1;88:106913. Epub 2020 Sep 1.

Department of Virology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran. Electronic address:

Background: The aim of this study was to determine the presence of HPV in patients with Prostate cancer (PCa) and its possible association with cancer progression.

Methods: In this case-control study, fresh prostate tissues and blood samples were collected from 90 individuals, including 58 cases samples with PCa and 32 non-malignant prostate tissue samples as a control group. The expression level of viral genes (E2, E6, and E7) and cellular factors including tumor suppressor proteins (Rb and p53), anti-apoptotic mediators (Bcl-2 and survivin), and some mediators involved in inflammation and angiogenesis was evaluated.

Results: The presence of the HPV genome was identified in 19 out of the 58 cases (32.7%) and five out of the 32 controls (15.6%). However, there was not any statistically significant relationship between the presence of the HPV genome and PCa (OR = 2.63, 95% C.I = 0.89-7.91, P-value = 0.078). Moreover, the HPV high-risk genotypes 16 and 18 were detected in 47.4% and 31.6% of HPV-infected PCa tissues, respectively. The expression level of the tumor suppressor proteins (Rb and p53) significantly decreased in the HPV-infected samples compared to the HPV negative specimens (P-value = 0.01, P-value = 0.01, respectively). However, the expression level of the anti-apoptotic mediators and those involved in angiogenesis and inflammation significantly increased in the HPV-infected PCa group compared to the HPV-negative PCa and control groups (P-value < 0.05, respectively).

Conclusion: Our study suggests that although it is not definitely known whether HPV causes PCa, this virus probably modulates PCa cell behavior by affecting inflammation, angiogenesis, and apoptosis mechanisms, which, in turn, promotes tumorigenesis.
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http://dx.doi.org/10.1016/j.intimp.2020.106913DOI Listing
November 2020

Molecular Epidemiology of Anellovirus Infection in Children's Urine: A Cross-sectional Study.

Adv Biomed Res 2020 22;9:16. Epub 2020 Apr 22.

Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran.

Background: Anelloviridae is a viral family which is considered as a constant component of human virome. Given the ubiquitous nature of the virus infection and the long-standing relationship between the virus and the host, in the present study, we aimed at investigating the presence of Anelloviruses in the urine samples of children in a cross-sectional study.

Materials And Methods: The urine samples of 50 children who were referred to Hazrat Ali Asghar Children's Hospital, affiliated to Iran University of Medical Sciences, Tehran, Iran, were obtained. Three TaqMan real-time polymerase chain reactions (PCRs) were carried out for Anellovirus detection. A phylogenetic tree was drawn for positive products after PCR amplification, purification, and nucleotide sequencing. SPSS, version 20, was used for statistical analyses.

Results: Children's mean age ± standard deviation was 4.30 ± 1.47 years and 56% (28/50) were female. Real-time PCR revealed that Anellovirus was positive in 12% (6/50). Furthermore, PCR-sequencing results showed that torque teno virus was detected in 83.3% (5/6) and SEN virus in 16.6% (1/6) of the Anellovirus positive samples. In addition, 86% (5/6) of the children with positive samples were female. No significant difference was detected between any of the demographic characteristics and Anellovirus positivity ( > 0.05).

Conclusion: According to our preliminary study, the presence of Anelloviruses in the urine samples of asymptomatic children in Iran is striking, although limited sample size and age range limitations might have affected the comprehensive results of our study.
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http://dx.doi.org/10.4103/abr.abr_169_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7282691PMC
April 2020

The role of human herpesvirus-6 and inflammatory markers in the pathogenesis of multiple sclerosis.

J Neuroimmunol 2020 Jul 4;346:577313. Epub 2020 Jul 4.

Department of Medical Virology, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran. Electronic address:

Multiple sclerosis (MS) is a destructive autoimmune neuroinflammatory and neurodegenerative disorder of the central nervous system (CNS) with unknown etiology and mechanism of pathogenesis. Pathogens, especially human herpes viruses, have been suggested as environmental factors of the MS and other neuroinflammatory disorders. This study aimed to determine the prevalence of HHV-6 antibody response in MS patients and investigate the levels of pro/anti-inflammatory cytokine and chemokines in MS patients in comparison with healthy subjects. Two hundred sixty-three patients with clinically defined MS (140 females and 123 males), along with 263 healthy subjects (140 females and 123 males), were recruited for this study. After the analysis of HHV-6 seropositivity/seronegativity, the levels of some pro/anti-inflammatory cytokines, including TNF-α, IFN-γ, IL-1β, IL-6, and IL-12 as well as two chemokines, namely CCL-2 and CCL-5 were determined by the enzyme-linked immunosorbent assay (ELISA) method in HHV-6 seropositive/seronegative MS patients and healthy subjects. Our results showed that the serum concentrations of TNF-α, IFN-γ, IL-1β, IL-6, and CCL-5 elevated in HHV-6 seropositive compared with seronegative MS patients (P < .05). Moreover, the levels of IL-12, IL-10, and CCL-2 levels were significantly lower in seropositive MS patients when compared with seronegative MS patients (P < .05). Also, our results revealed that the mean values of the expanded disability status scale (EDSS) were significantly higher in HHV-6 seropositive versus seronegative MS patients (P < .05). In conclusion, we proposed that HHV-6 infection may play a role in MS pathogenesis by changing cytokine signaling in MS patients that may lead to peripheral inflammation.
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http://dx.doi.org/10.1016/j.jneuroim.2020.577313DOI Listing
July 2020

Investigation of gene mutations and expression in hepatocellular carcinoma and cirrhosis in association with hepatitis B virus infection.

Infect Agent Cancer 2020 3;15:37. Epub 2020 Jun 3.

Department of Virology, Iran University of Medical Sciences, Tehran, Iran.

Hepatitis B virus (HBV), along with Hepatitis C virus chronic infection, represents a major risk factor for hepatocellular carcinoma (HCC) development. However, molecular mechanisms involved in the development of HCC are not yet completely understood. Recent studies have indicated that mutations in gene encoding for β-catenin protein lead to aberrant activation of the Wnt/ β-catenin pathway. The mutations in turn activate several downstream genes, including , promoting the neoplastic process. The present study evaluated the mutational profile of the gene and expression levels of and genes in HBV-related HCC, as well as in cirrhotic and control tissues. Mutational analysis of the β-catenin gene and HBV genotyping were conducted by direct sequencing. Expression of β-catenin and genes was assessed using real-time PCR. Among the HCC cases, 18.1% showed missense point mutation in exon 3 of , more frequently in codons 32, 33, 38 and 45. The frequency of mutation in the hotspots of exon 3 was significantly higher in non-viral HCCs (29.4%) rather than HBV-related cases (12.7%,  = 0.021). The expression of β-catenin and genes was found upregulated in cirrhotic tissues in association with HBV infection. Mutations at both phosphorylation and neighboring sites were associated with increased activity of the Wnt pathway. The results demonstrated that mutated β-catenin caused activation of the Wnt pathway, but the rate of gene mutations was not related to HBV infection. HBV factors may deregulate the Wnt pathway by causing epigenetic alterations in the HBV-related HCC.
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http://dx.doi.org/10.1186/s13027-020-00297-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7268324PMC
June 2020

SARS-CoV-2 Molecular and Phylogenetic analysis in COVID-19 patients: A preliminary report from Iran.

Infect Genet Evol 2020 10 30;84:104387. Epub 2020 May 30.

Department of Virology, Iran University of Medical Sciences, Tehran, Iran; Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran. Electronic address:

Background: The aim of the current study was to investigate and track the SARS-CoV-2 in Iranian Coronavirus Disease 2019 (COVID-19) patients using molecular and phylogenetic methods.

Methods: We enrolled seven confirmed cases of COVID-19 patients for the phylogenetic assessment of the SARS-CoV-2 in Iran. The nsp-2, nsp-12, and S genes were amplified using one-step RT-PCR and sequenced using Sanger sequencing method. Popular bioinformatics software were used for sequences alignment and analysis as well as phylogenetic construction.

Results: The mean age of the patients in the present study was 60.42 ± 9.94 years and 57.1% (4/7) were male. The results indicated high similarity between Iranian and Chinese strains. We could not find any particular polymorphisms in the assessed regions of the three genes. Phylogenetic trees by neighbor-joining and maximum likelihood method of nsp-2, nsp-12, and S genes showed that there are not any differences between Iranian isolates and those of other countries.

Conclusion: As a preliminary phylogenetic study in Iranian SARS-CoV-2 isolates, we found that these isolates are closely related to the Chinese and reference sequences. Also, no sensible differences were observed between Iranian isolates and those of other countries. Further investigations are recommended using more comprehensive methods and larger sample sizes.
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http://dx.doi.org/10.1016/j.meegid.2020.104387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7832360PMC
October 2020

Anti-cancer effects of Bifidobacterium species in colon cancer cells and a mouse model of carcinogenesis.

PLoS One 2020 13;15(5):e0232930. Epub 2020 May 13.

Microbial Biotechnology Research Centre, Iran University of Medical Sciences, Tehran, Iran.

Introduction: Probiotics are suggested to prevent colorectal cancer (CRC). This study aimed to investigate the anticancer properties of some potential probiotics in vitro and in vivo.

Materials And Methods: Anticancer effects of the following potential probiotic groups were investigated in LS174T cancer cells compared to IEC-18 normal cells. 1. a single strain of Bifidobacterium. breve, 2. a single strain of Lactobacillus. reuteri, 3. a cocktail of 5 strains of Lactobacilli (LC), 4. a cocktail of 5 strains of Bifidobacteria (BC), 5. a cocktail of 10 strains from Lactobacillus and Bifidobacterium (L+B). Apoptosis rate, EGFR, HER-2 and PTGS-2 (COX-2 protein) expression levels were assessed as metrics of evaluating anticancer properties. Effect of BC, as the most effective group in vitro, was further assessed in mice models.

Results: BC induced ~21% and only ~3% apoptosis among LS174T and IEC-18 cells respectively. BC decreased the expression of EGFR by 4.4 folds, HER-2 by 6.7 folds, and PTGS-2 by 20 folds among the LS174T cells. In all these cases, BC did not interfere significantly with the expression of the genes in IEC-18 cells. This cocktail has caused only 1.1 folds decrease, 1.8 folds increase and 1.7 folds decrease in EGFR, HER-2 and PTGS-2 expression, respectively. Western blot analysis confirmed these results in the protein level. BC significantly ameliorated the disease activity index, restored colon length, inhibited the increase in incidence and progress of tumors to higher stages and grades.

Conclusions: BC was the most efficient treatment in this study. It had considerable "protective" anti-cancer properties and concomitantly down regulated EGFR, HER-2 and PTGS-2 (COX-2), while having significant anti-CRC effects on CRC mice models. In general, this potential probiotic could be considered as a suitable nutritional supplement to treat and prevent CRC.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0232930PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7219778PMC
July 2020

Occult HCV and occult HBV coinfection in Iranian human immunodeficiency virus-infected individuals.

J Med Virol 2020 Mar 31. Epub 2020 Mar 31.

Research Center of Pediatric Infectious Diseases, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran.

The presence of hepatitis C virus (HCV) genome in liver biopsy or peripheral blood mononuclear cell (PBMC) specimens in the absence of detectable HCV-RNA in plasma of the people with or without anti-HCV antibodies has defined as occult HCV infection (OCI), whereas occult hepatitis B virus infection (OBI) is detection of hepatitis B virus (HBV) genome in the absence of traceable hepatitis B surface antigen in the plasma samples of patients. The purpose of this study is to determine the presence of OBI and OCI in human immunodeficiency virus (HIV)-infected individuals. In this cross-sectional research, 190 Iranian HIV-infected individuals were enrolled from September 2015 to February 2019. All participants were tested regarding various serological markers for HCV and HBV infections. Viral RNA and DNA were extracted from plasma and PBMC specimens, and the presence of HCV-RNA in plasma and PBMC samples was tested using reverse transcriptase-nested polymerase chain reaction (PCR), HBV viral load was determined in plasma samples using COBAS TaqMan 48 Kit, and also the presence of the HBV-DNA in PBMC samples was tested by real-time PCR. In this study, the prevalence of OBI and OCI in HIV-infected individuals was 3.1% and 11.4%, respectively. The genotypes of HCV in the patients with OCI were as follows: 57.1% were infected with subtype 3a, 35.7% were infected with subtype 1a, and 7.1% was infected with subtype 1b. It is noteworthy that in this study, two patients (1.1%) had OCI/OBI coinfections. The present study revealed that 1.1% of Iranian HIV-infected individuals had OBI and OCI at the same time. Therefore, it seems that designing prospective surveys to determine the presence of this coinfection in HIV-infected individuals is informative.
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http://dx.doi.org/10.1002/jmv.25808DOI Listing
March 2020

Molecular Epidemiology of Epstein-Barr virus (EBV) in Patients with Hematologic Malignancies.

Asian Pac J Cancer Prev 2020 Mar 1;21(3):693-698. Epub 2020 Mar 1.

Department of Virology, Iran University of Medical Sciences, Tehran, Iran.

Background: Epstein-Barr virus (EBV) is associated with different malignant diseases, such as Hodgkin lymphoma (HL) and lymphoproliferative disorders. Patients with hematologic malignancies by variable severity could be suspected for the infection with different types of this virus. This preliminary study reported the genotyping and related viral load of Epstein-Barr virus in Iranian patients with hematologic malignancies for estimation of possible factors affecting malignancy.

Methods: Peripheral blood mononuclear cells (PBMC) of HL (n=20), NHL (n=29), acute lymphocytic leukemia (ALL) (n=18) and chronic lymphocytic leukemia (CLL) (n=12) were obtained. After DNA extraction, a nested-PCR and a conventional-PCR targeting EBNA-2 and EBNA-3C genes were performed. A real-time PCR assay for viral load quantitation carried out. Standard curve analysis used for evaluation of amplification specificity.

Results: Of 79 included patients, 34 (43%) were EBV positive. There were 23.5% (8/34), 38.2% (13/34), 23.5% (8/34), 14.8% (5/34) in HL, NHL, ALL and CLL groups, respectively. Also, the main genotype was genotype I (91.2%) which it follows by 8.8% (3/34) genotype II. The real-time PCR assay showed the mean viral load ± std. deviation was 2.75×105 ± 1.202×106 copies/μg DNA and the higher viral load was seen in NHL patients.

Conclusion: This preliminary investigation in Iran shows that the main EBV genotype into our region probably is genotype I (91.2%) which it is similar to others. We could not find any statistically significant association between the virus infection and viral load with any specific disease and patients' demographic data. 
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http://dx.doi.org/10.31557/APJCP.2020.21.3.693DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7437315PMC
March 2020

HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naïve HIV-infected individuals.

PLoS One 2020 2;15(3):e0229275. Epub 2020 Mar 2.

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

Background: The presence of drug resistance mutations (DRMs) against antiretroviral agents is one of the main concerns in the clinical management of individuals with human immunodeficiency virus-1 (HIV-1) infection, especially in regions of the world where treatment options are limited. The current study aimed at assessing the prevalence of HIV-1 DRMs among naïve and treatment-experienced HIV-1-infected patients in Iran.

Methods: From April 2013 to September 2018, the HIV-1 protease and reverse transcriptase genes were amplified and sequenced in plasma specimens of 60 newly diagnosed antiretroviral-naive individuals and 46 participants receiving antiretroviral therapies (ARTs) for at least six months with an HIV viral load of more than 1000 IU/mL to determine the HIV-1 DRMs and subtypes.

Results: Among the 60 treatment-naïve HIV-1-infected participants, 8.3% were infected with HIV-1 variants with surveillance DRMs (SDRMs). The SDRMs, D67N and D67E, belonged to the NRTIs class in two patients and K103N and V106A belonged to the NNRTIs class in three patients. The phylogenetic analysis showed that 91.7% of the subjects were infected with subtype CRF35_AD, followed by subtype B (5.0%) and CRF01_AE (3.3%). Among the 46 ART-experienced participants, 33 (71.7%) carried HIV-1 variants with SDRMs (9.1% against PIs, 78.8% against NRTIs, and 100% against NNRTIs). M46I and I47V were the most common mutations for PIs, M184V was the most common mutation for the NRTIs, and K103N/S was the most common mutation for NNRTIs. Phylogenetic analysis of the polymerase region showed that all of the 46 HIV-1-infected patients who failed on ART carried CRF35_AD.

Conclusions: The moderate prevalence of SDRMs (8.3%) in treatment-naïve and ART-failed (77.1%) Iranian patients with HIV-1-infection emphasizes the need for systematic viral load monitoring, expanding drug resistance testing, carefully surveilling individuals on ART regimens, and facilitating access to new antiretrovirals by health authorities.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0229275PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7051075PMC
June 2020

Maraviroc attenuates the pathogenesis of experimental autoimmune encephalitis.

Int Immunopharmacol 2020 Mar 30;80:106138. Epub 2020 Jan 30.

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

It has been shown that the blockade of chemokine receptor type 5 can dampen inflammatory reaction within the central nervous system (CNS). In the present study, we utilized maraviroc, a potent antagonist o CCR5, to examine whether this drug can mitigate neuroinflammation in the spinal cord of mice induced by experimental autoimmune encephalitis (EAE), considered a murine model of multiple sclerosis (MS). For this aim, mice were immunized with myelin oligodendrocyte glycoprotein 35-55 (MOG35-55), followed by pertussis toxin to induce paralysis in EAE mice. The animals intraperitoneally received various doses of maraviroc (5, 25, and 50 mg/kg body weight) when the early clinical signs of EAE appeared. The results demonstrated that the administration of maraviroc led to a marked decrease in the clinical score and improvement in behavioral motor functions. Moreover, our finding indicated that the administration of maraviroc significantly attenuates the infiltration of inflammatory cells to the spinal cord, microgliosis, astrogliosis, pro-inflammatory cytokines, and cell death in EAE mice. The flow cytometry data indicated that a decreased number of CD4+ and CD8+ T cells in the peripheral blood of mice with EAE without affecting the number of T regulatory cells (CD4 + CD25+ forkhead box protein 3+). Finally, it seems that maraviroc is well-tolerated, and targeting CCR5 could open up a new horizon in the treatment of MS.
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http://dx.doi.org/10.1016/j.intimp.2019.106138DOI Listing
March 2020

Oncolytic Newcastle disease virus reduces growth of cervical cancer cell by inducing apoptosis.

Saudi J Biol Sci 2020 Jan 23;27(1):47-52. Epub 2019 Apr 23.

Department of Virology, Pasteur Institute of Iran, Tehran, Iran.

Although Oncolytic viruses have been regarded as a promising tool for targeted therapy of cancer, accomplishing high efficacy and specificity with this strategy is challenging. Oncolytic virotherapy is one of the novel therapeutic methods recently used for the therapy of human malignancies. Cervical cancer is on the major public health problem and the second most common cause of cancer death among females in less developed countries. The aim of this study was mainly to determine the apoptosis effect of oncolytic Newcastle disease virus (NDV) in TC-1 cell line. In the current study, the oncolytic NDV, vaccine strain LaSota, was used to infect murine TC-1 cells of human papillomavirus (HPV)-associated carcinoma which expressing human papillomavirus 16 (HPV-16) E6/E7 antigens in vitro. The effectiveness of NDV for cervical cancer cell line was investigated by evaluating the antitumor activity of oncolytic NDV and the involved mechanisms. Antitumor activities of oncolytic NDV were assessed by cell proliferation (MTT) and lactate dehydrogenase (LDH) release analysis. In addition, molecular changes of early stage of apoptosis and the role of reactive oxygen species (ROS) were analyzed by flow cytometry and Western Blot in NDV-treated TC-1 cells. The results showed that NDV treatment significantly decreased the viability of a TC-1 cell line and suppressed the growth by inducing apoptotic cell death. In addition, we demonstrated that NDV-induced apoptosis of TC-1 cells is mediated by ROS production. In summary, our findings suggest that oncolytic NDV is a possible therapeutic candidate as a selective antitumor agent for the treatment of cervical cancer.
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http://dx.doi.org/10.1016/j.sjbs.2019.04.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6933251PMC
January 2020

Evaluation of CCR5-Δ32 mutation among individuals with high risk behaviors, neonates born to HIV-1 infected mothers, HIV-1 infected individuals, and healthy people in an Iranian population.

J Med Virol 2020 08 17;92(8):1158-1164. Epub 2020 Jan 17.

Research Center of Pediatric Infectious Diseases, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran.

One of the important genetic factors related to resistance to HIV-1 infection is the presence of the C-C chemokine receptor type 5 delta 32 (CCR5-Δ32) homozygous genotype (Δ32/Δ32). The aim of this study was to evaluate the CCR5-Δ32 mutation among individuals with high-risk behaviors, neonates born to HIV-1-infected mothers in the prevention of mother-to-child transmission (PMTCT) project, HIV-1-infected individuals, and healthy people. The frequency of the CCR5-Δ32 genotype was assessed in a cross-sectional survey carried out from March 2014 to March 2019 among four different groups of the Iranian population. Genomic DNA was extracted from peripheral blood mononuclear cells of 140 Iranian healthy people, 84 neonates born to HIV-1-infected mothers in the PMTCT project, 71 people with high-risk behaviors, and 76 HIV-1-infected individuals. The polymerase chain reaction method was used for the amplification of the CCR5 gene. The CCR5-Δ32 heterozygous deletion was detected in five (6.6%) HIV-1-infected individuals, four (4.7%) neonates born to HIV-1 positive mothers, two (1.4%) healthy people, and also three (4.2%) people with high-risk behaviors whereas the CCR5-Δ32 homozygous deletion was absent in all the groups (Fisher's exact test, P = .0242). The allele of CCR5-Δ32 homozygous was not detected in the four study groups, and no significant difference was seen in the frequency of the CCR5Δ32 heterozygous allele between HIV seropositive and seronegative individuals. Therefore, it seems that this allele alone cannot explain the natural resistance to HIV-1 infection and probably several mechanisms are responsible for these processes and it should be further investigated.
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http://dx.doi.org/10.1002/jmv.25658DOI Listing
August 2020

HIV-1 Tat protein attenuates the clinical course of experimental autoimmune encephalomyelitis (EAE).

Int Immunopharmacol 2020 Jan 9;78:105943. Epub 2019 Dec 9.

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

A growing body of evidence has shown that the human immunodeficiency virus (HIV) infection is associated with a significantly decreased risk of developing multiple sclerosis (MS) in patients with acquired immunodeficiency virus (AIDS). It is thought that two mechanisms are in charge of protection against MS, which include immunosuppression induced by chronic HIV infection (depletion of CD4 + T cells) and antiretroviral medications. HIV-1 encodes several regulatory (Tat and Rev) and accessory (Vpr, Vif, Vpu, and Nef) proteins that have immunosuppressive and immunomodulatory properties. HIV-1 Tat protein is a strongly immunosuppressive agent and can cross the blood-brain barrier (BBB). In this study, we examined the effect of HIV-1 Tat, which is classified into clade B and C, on inflammation, gliosis, apoptosis, and behavioral function in a murine model of MS called experimental autoimmune encephalomyelitis (EAE). For this aim, mice were immunized with myelin oligodendrocyte glycoprotein 35-55 (MOG35-55), followed by pertussis toxin to induce paralysis in EAE mice. After the induction of EAE in mice, the animals intraperitoneally received serial doses of HIV-1 Tat clade B and C (5, 10, and 20 µg/kg body weight) when the early clinical manifestations of EAE were initiated. The results showed that the administration of both clades of the Tat protein led to a marked decrease in the clinical score of EAE mice, as well as improvement in motor-neuron functions. In line with this, Tat considerably reduced the number of apoptotic cells in the sacral region of the spinal cord through the upregulation expression of the Bcl-2 protein. Besides, proinflammatory cytokines such as, IFN-γ, TNF-α, IL-6, and IL-17 were significantly diminished in the serum and spinal cord of EAE mice receiving HIV-1 Tat clade B and C. Conversely, anti-inflammatory cytokines, including IL-10 and IL-4 were elevated in the serum and spinal cord of EAE mice receiving HIV Tat clade B and C when compared with the control group. The immunohistochemical analysis indicated that HIV-1 Tat clade B and C mitigated microgliosis and astrogliosis. The flow cytometry analysis demonstrated that the number of Th1 and Th17cells was significantly decreased in response to TAT administration while the frequency of Th2 cells was markedly increased in the peripheral blood of mice with EAE without influencing the number of T regulatory cells (CD4 + CD25 + forkhead box protein 3 + ). It seems that HIV-1 Tat could be a bona fide therapeutic protein for the alleviation of MS since it has beneficial roles in the suppression of neuroinflammation in MS pathology.
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http://dx.doi.org/10.1016/j.intimp.2019.105943DOI Listing
January 2020

Molecular evidence of human papillomaviruses in the retinoblastoma tumor.

Virusdisease 2019 Sep 24;30(3):360-366. Epub 2019 Jul 24.

4Department of Pathology, Rassoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran.

Retinoblastoma tumor (RB) is one of the most prevalent ocular cancers among children. RB may be caused by inherited mutations in gene as well as some environmental risk factors. Human papillomaviruses (HPV) are suspected as a risk factor of RB due to their pRb inactivating protein. This study evaluated the molecular prevalence of HPV among the RB tumor specimens in Iran. The RB tumor samples were tested for detection of HPV-L1 gene using a nested-PCR approach, and then followed by sequencing and phylogenetic analysis to reveal HPV types. Overall, there were 61 RB tumor samples; 54/61 (88.5%) had unilateral and 7/61 (11.5%) bilateral RB; 55/61 cases (90.2%) had sporadic non-familial RB tumor. HPV-DNA was detected in 6/61 (9.8%) of patients' tumors; the HPV positive RB cases all had unilateral and unfamiliar sporadic RB tumor. HPV type 16 was the most prevalent type identified across the RB tumor samples (3/61, 4.9%). The rate of detected HPV among the RB specimens seems to be considerable. Further investigations are required to elucidate the exact association between HPV and progression to RB.
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http://dx.doi.org/10.1007/s13337-019-00540-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6863999PMC
September 2019

HIV-1 integrase drug-resistance mutations in Iranian treatment-experienced HIV-1-infected patients.

Arch Virol 2020 Jan 18;165(1):115-125. Epub 2019 Nov 18.

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

The latest class of antiretrovirals (ARVs), including integrase strand transfer inhibitors (INSTIs), has been demonstrated to be effective for antiretroviral therapy (ART). Despite all the distinguishing characteristics of these drugs, including a high genetic barrier to resistance and lower toxicity than other ARVs, unfortunately, INSTI drug resistance mutations (DRMs) have occasionally been observed. The aim of this study was to investigate the presence of DRMs associated with INSTIs among treatment-experienced HIV-1-infected patients. From June 2012 to December 2018, a total of 655 treatment-experienced HIV-1-infected patients enrolled in this cross-sectional survey. Following amplification and sequencing of the HIV-1 integrase region of the pol gene, DRM and phylogenetic analysis were successfully carried out on the plasma samples of patients who had a viral load over 1,000 IU/ml after at least 6 months of ART. Out of the 655 patients evaluated, 62 (9.5%) had a viral load higher than 1,000 IU/ml after at least 6 months of ART. Phylogenetic analysis showed that all of the 62 HIV-1 patients experiencing treatment failure were infected with CRF35_AD, and one of these patients (1.6%) was infected with HIV-1 variants with DRMs. The DRMs that were identified belonged to the INSTI class, including E138K, G140A, S147G, and Q148R. This survey shows that DRMs belonging to the INSTI class were detected in an Iranian HIV patient who has experienced treatment failure. Therefore, regarding the presence of DRMs to INSTIs in ART-experienced patients, it seems better to perform drug resistance mutation testing in HIV patients experiencing treatment failure before changing the ART regimen and prescribing this class of medication.
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http://dx.doi.org/10.1007/s00705-019-04463-yDOI Listing
January 2020

Epstein-Barr virus molecular epidemiology and variants identification in head and neck squamous cell carcinoma.

Eur J Cancer Prev 2020 11;29(6):523-530

Department of Virology, Iran University of Medical Sciences, Tehran, Iran.

Epstein-Barr virus (EBV) is known as one of the most widespread oncogenic viruses. Head and neck squamous cell carcinoma (HNSCC) is triggered by various risk factors. The aim of the present study was to determine the EBV infection rate, genotyping and variants frequency in HNSCC patients. In this cross-sectional study, 156 patients with HNSCC were enrolled. Formalin fixed paraffin embedded (FFPE) tissue samples were selected from hospitals affiliated to Iran University of Medical Sciences, Tehran, Iran. The EBV EBNA-3C, EBNA-1 and LMP-1 genes were amplified by PCR and then analyzed and confirmed by nucleotide sequencing. CLC work bench 5, MEGA6 and SPSS v.21 software were used for analysis the raw data. The mean age ± SD (years) of the all patients (n = 156) was 60.5 ± 12.6, in which of 121(77.6%) males it was 60.7 ± 11.9 and of 35 (22.4%) females it was 59.7 ± 14.9. Totally, 20 samples (12.8%) were found to be infected with EBV genome. The EBV genotypes 1 and 2 were calculated 90% (18/20) and 10% (2/20), respectively. vLMP-1 found in 40% (4/10) of all LMP-1 tested samples. Furthermore, the EBNA-1 predominant variants were P-ala followed by P-thr and also there were three P-ala-v2 sub variants. Statistics could not find any significant associations although there were some potentials. By our preliminary study in Iran, it revealed that EBV-1 is the predominant Epstein-Barr virus genotype in head and neck squamous cell carcinoma patients. vLMP-1 isolates showed lower survival rate than others. EBNA-1 variants had no significant association with any specific disease complication.
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http://dx.doi.org/10.1097/CEJ.0000000000000554DOI Listing
November 2020

The Frequency of HIV-1 Infection in Iranian Children and Determination of the Transmitted Drug Resistance in Treatment-Naïve Children.

Curr HIV Res 2019 ;17(6):397-407

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

Background: The advent of resistance-associated mutations in HIV-1 is a barrier to the success of the ARTs.

Objective: In this study, the abundance of HIV-1 infection in Iranian children, and also detection of the TDR in naïve HIV-1 infected pediatric (under 12 years old) were evaluated.

Materials: From June 2014 to January 2019, a total of 544 consecutive treatment-naïve HIV-1- infected individuals enrolled in this study. After RNA extraction, amplification, and sequencing of the HIV-1 pol gene, the DRM and phylogenetic analysis were successfully performed on the plasma specimens of the ART-naïve HIV-1-infected-children under 12 years old. The DRMs were recognized using the Stanford HIV Drug Resistance Database.

Results: Out of the 544 evaluated treatment-naïve HIV-1-infected individuals, 15 (2.8%) cases were children under 12 years old. The phylogenetic analyses of the amplified region of pol gene indicated that all of the 15 HIV-1-infected pediatric patients were infected by CRF35_AD, and a total of 13.3% (2/15) of these children were infected with HIV-1 variants with SDRMs (one child harbored two related SDRMs [D67N, V179F], and another child had three related SDRMs [M184V, T215F, and K103N]), according to the last algorithm of the WHO. No PIs-related SDRMs were observed in HIV-1-infected children.

Conclusion: The current study demonstrated that a total of 13.3% of treatment-naïve HIV-1-infected Iranian pediatrics (under 12 years old) were infected with HIV-1 variants with SDRMs. Therefore, it seems that screening to recognize resistance-associated mutations before the initiation of ARTs among Iranian children is essential for favorable medication efficacy and dependable prognosis.
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http://dx.doi.org/10.2174/1570162X17666191106111211DOI Listing
January 2021

Inhibition of H1N1 influenza virus infection by zinc oxide nanoparticles: another emerging application of nanomedicine.

J Biomed Sci 2019 Sep 10;26(1):70. Epub 2019 Sep 10.

Department of Medical Virology, Iran University of Medical Sciences, Tehran, Iran.

Background: Currently available anti-influenza drugs are often associated with limitations such as toxicity and the appearance of drug-resistant strains. Therefore, there is a pressing need for the development of novel, safe and more efficient antiviral agents. In this study, we evaluated the antiviral activity of zinc oxide nanoparticles (ZnO-NPs) and PEGylated zinc oxide nanoparticles against H1N1 influenza virus.

Methods: The nanoparticles were characterized using the inductively coupled plasma mass spectrometry, x-ray diffraction analysis, and electron microscopy. MTT assay was applied to assess the cytotoxicity of the nanoparticles, and anti-influenza activity was determined by TCID50 and quantitative Real-Time PCR assays. To study the inhibitory impact of nanoparticles on the expression of viral antigens, an indirect immunofluorescence assay was also performed.

Results: Post-exposure of influenza virus with PEGylated ZnO-NPs and bare ZnO-NPs at the highest non-toxic concentrations could be led to 2.8 and 1.2 log10 TCID50 reduction in virus titer when compared to the virus control, respectively (P < 0.0001). At the highest non-toxic concentrations, the PEGylated and unPEGylated ZnO-NPs led to inhibition rates of 94.6 and 52.2%, respectively, which were calculated based on the viral loads. There was a substantial decrease in fluorescence emission intensity in viral-infected cell treated with PEGylated ZnO-NPs compared to the positive control.

Conclusions: Taken together, our study indicated that PEGylated ZnO-NPs could be a novel, effective, and promising antiviral agent against H1N1 influenza virus infection, and future studies can be designed to explore the exact antiviral mechanism of these nanoparticles.
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http://dx.doi.org/10.1186/s12929-019-0563-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6734352PMC
September 2019

High prevalence of occult hepatitis C virus infection in injection drug users with HIV infection.

Arch Virol 2019 Oct 25;164(10):2493-2504. Epub 2019 Jul 25.

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

One of the pathological forms of chronic hepatitis C is occult HCV infection (OCI), in which there is no detectable HCV RNA in plasma specimens but HCV RNA is present in PBMCs and liver biopsy specimens. The aim of this study is to estimate the prevalence of OCI in HIV-positive people who are injection drug users (IDUs). From April 2015 to August 2018, 161 Iranian IDUs with HIV infection enrolled in the study. Viral RNA was extracted from plasma and PBMC samples of participants, and the presence of HCV RNA was examined using RT nested PCR with primers from two conserved regions (5´-UTR and NS5B). HCV genotyping was performed using RFLP and sequencing methods. Of the 161 patients, 134 (83.2%) were positive for anti-HCV antibodies. All 27 patients who were negative for anti-HCV were also negative for HCV RNA in plasma, but five of them (18.5%) were positive for HCV RNA in PBMCs. Importantly, 9 out of 50 patients (18.0%) who apparently had recovered from HCV infection (i.e., were anti-HCV positive and HCV RNA negative) were positive for HCV RNA in PBMCs. Overall, 18.1% of the patients who had no signs of previous HCV infection or had apparently recovered from the disease had OCI. The HCV genotypes of the cases with OCI were as follows: five patients (35.7%) were infected with subtype 1a, eight patients (57.1%) were infected with subtype 3a, and one patient (7.1%) was infected with genotype 4. Thus, it seems that the prevalence of OCI in HIV-positive IDUs is extremely significant in Iran and is likely to delay the global eradication of HCV infection until 2030.
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http://dx.doi.org/10.1007/s00705-019-04353-3DOI Listing
October 2019

The frequency of varicella-zoster virus infection in patients with multiple sclerosis receiving fingolimod.

J Neuroimmunol 2019 03 26;328:94-97. Epub 2018 Dec 26.

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

Multiple Sclerosis (MS) is thought to be an autoimmune disease of the central nervous system (CNS), in which the immune system becomes activated, cross the blood-brain barrier (BBB), and cause neuroinflammation and neurodegeneration. Fingolimod is considered a disease-modifying therapy (DMT), possessing immunomodulatory effects on the immune system, especially autoreactive T cells being licensed in lymph nodes. Although the fidelity of the drug is undeniable in the management of disease course, various adverse effects have been reported in some patients taking this medication. In this study, 420 MS patients, consisted of 210 patients receiving interferon-beta (IFN-beta) and 210 patients receiving fingolimod therapies. As a control group, 210 age- and sex-matched healthy individuals were recruited in our study. The levels of anti-VZV IgG and IgM were determined using enzyme-linked immunosorbent assay (ELISA). The presence of VZV DNA in peripheral blood mononuclear cells (PBMCs) was also investigated using the PCR method. The percentage of seropositivity for anti-VZV IgG and anti-VZV IgM in MS patients was 94.8% and 0%, respectively in those taking fingolimod therapy. In patients receiving IFN-beta, the rate of seropositivity for anti-VZV IgG and anti-VZV IgM was 93.8% and 0%, respectively. In healthy individuals, the rate of seropositivity for anti-VZV IgG and anti-VZV IgM was 84.3% and 0%, respectively. The PCR results showed that 7.6% of patients receiving fingolimod were positive for VZV DNA, while none of the healthy subjects nor MS patients taking IFN-beta were positive for DNA of VZV. The statistical analysis indicated that the frequency of VZV DNA in patients receiving fingolimod was significantly (p = .00) higher than MS patients taking IFN-beta and healthy subjects. It seems that the use of fingolimod should be carefully prescribed as the occurrence of VZV infection/reactivation is increased in comparison to other MS patients who receive different therapy.
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http://dx.doi.org/10.1016/j.jneuroim.2018.12.009DOI Listing
March 2019

Rotavirus Infection Enhances Levels of Autoantibodies Against Islet Cell Antigens GAD65 and IA-2 in Children with Type 1 Diabetes.

Fetal Pediatr Pathol 2019 Apr 27;38(2):103-111. Epub 2018 Dec 27.

a Department of Virology , Faculty of Medicine, Iran University of Medical Sciences , Tehran , The Islamic Republic of Iran.

Background: Some studies implicate rotavirus infection as a trigger for the development of type 1 diabetes mellitus (T1DM) in children, however findings are controversial.

Objectives: We investigated the link between rotavirus infection and autoantibodies against islet antigens and T1DM in children.

Methods: Serum samples from 80 new-onset diabetic and 80 nondiabetic children were screened for anti-rotavirus IgG, anti-GAD65 and anti-IA-2 autoantibodies using ELISA kits.

Results: Positivity percentages of anti-rotavirus IgG detection in diabetic and nondiabetic children were 51.3% and 35.0%, respectively (p = 0.03). The mean anti-GAD65 and anti-IA-2 antibody titers in anti-rotavirus IgG positive samples were statistically higher than that the anti-rotavirus IgG negative samples. A positive correlation was found between anti-rotavirus IgG and anti-GAD65 antibody levels (p = 0.004; r = 0.22).

Conclusions: Our findings support the hypothesis that rotovirus infection may induce T1DM in children.
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http://dx.doi.org/10.1080/15513815.2018.1547338DOI Listing
April 2019