Publications by authors named "Farhad Rezaei"

34 Publications

Seroprevalence Study on West Nile Virus (WNV) Infection, a Hidden Viral Disease in Fars Province, Southern Iran.

J Arthropod Borne Dis 2020 Jun 30;14(2):173-184. Epub 2020 Jun 30.

Department of Medical Entomology and Vector Control, School of Health, Shiraz University of Medical Sciences, Shiraz, Iran.

Background: West Nile Virus, a mosquito-borne flavivirus, causes a variety of symptoms in human, from asymptomatic infection to neuroinvasive disease. Several studies have been conducted on the seroprevalence of WNV infection in different areas from Iran. This study was performed to find the presence of antiviral antibodies in human serum among some high risk population and awareness of health care staff about symptom of the WNV infection.

Methods: Study performed in five geographical districts based on high population of immigrant and domestic birds and prevalence of the antiviral antibodies in horses which was reported previously. Totally 150 human blood samples were collected during 2018. The samples collected from patients referred to the clinics. The ELISA method used to detect IgG and IgM antibody against WNV. Logistic regression models used to analyze the effect of sex, age, keeping birds and urban/rural residence on the risk of infection. The awareness of health care staff about symptom of infection surveyed.

Results: From all blood donors, 41 samples (27.33%) showed positive to IgG antibody. From which 56.10% were males and remaining females. None of the mentioned factors had a significant relationship. Health care staff had less attention to the infection.

Conclusion: Although the prevalence of antibodies was relatively high, due to the similarity to other viral diseases, health care staff had less attention to the disease. The study showed that people in these areas have been exposed to the virus. Further research activities are recommended for control of this arbovirus.
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http://dx.doi.org/10.18502/jad.v14i2.3735DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738928PMC
June 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

CAR T cells: Living HIV drugs.

Rev Med Virol 2020 Nov 26;30(6):1-14. Epub 2020 Jul 26.

Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran.

Human immunodeficiency virus type 1 (HIV-1), the virus that causes AIDS (acquired immunodeficiency syndrome), is a major global public health issue. Although the advent of combined antiretroviral therapy (ART) has made significant progress in inhibiting HIV replication in patients, HIV-infected cells remain the principal cellular reservoir of HIV, this allows HIV to rebound immediately upon stopping ART, which is considered the major obstacle to curing HIV infection. Chimeric antigen receptor (CAR) cell therapy has provided new opportunities for HIV treatment. Engineering T cells or hematopoietic stem cells (HSCs) to generate CAR T cells is a rapidly growing approach to develop an efficient immune cell to fight HIV. Herein, we review preclinical and clinical data available for the development of CAR T cells. Further, the advantages and disadvantages of clinical application of anti-HIV CAR T cells will be discussed.
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http://dx.doi.org/10.1002/rmv.2139DOI Listing
November 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

Metabolic host response and therapeutic approaches to influenza infection.

Cell Mol Biol Lett 2020 5;25:15. Epub 2020 Mar 5.

4Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Based on available metabolomic studies, influenza infection affects a variety of cellular metabolic pathways to ensure an optimal environment for its replication and production of viral particles. Following infection, glucose uptake and aerobic glycolysis increase in infected cells continually, which results in higher glucose consumption. The pentose phosphate shunt, as another glucose-consuming pathway, is enhanced by influenza infection to help produce more nucleotides, especially ATP. Regarding lipid species, following infection, levels of triglycerides, phospholipids, and several lipid derivatives undergo perturbations, some of which are associated with inflammatory responses. Also, mitochondrial fatty acid β-oxidation decreases significantly simultaneously with an increase in biosynthesis of fatty acids and membrane lipids. Moreover, essential amino acids are demonstrated to decline in infected tissues due to the production of large amounts of viral and cellular proteins. Immune responses against influenza infection, on the other hand, could significantly affect metabolic pathways. Mainly, interferon (IFN) production following viral infection affects cell function via alteration in amino acid synthesis, membrane composition, and lipid metabolism. Understanding metabolic alterations required for influenza virus replication has revealed novel therapeutic methods based on targeted inhibition of these cellular metabolic pathways.
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http://dx.doi.org/10.1186/s11658-020-00211-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7059726PMC
November 2020

Seroepidemiology of dengue and chikungunya fever in patients with rash and fever in Iran, 2017.

Epidemiol Infect 2020 02 26;148:e42. Epub 2020 Feb 26.

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

After the mass campaign of Measles and Rubella vaccination in 2003 in Iran, the cases of measles and rubella infection decreased but still, the cases of rash and fever were reported. It is worth noting that some other viral infections show signs similar to measles and rubella such as some arboviruses. Considering the epidemic outbreak of arbovirus infections in countries neighbouring Iran, we performed this study to estimate the possibility of chikungunya and dengue fever among measles and rubella IgM negative patients presenting with rash and fever from December 2016 to November 2017 in the National Measles Laboratory at Tehran University of Medical Sciences. Serum samples were selected at random from patients from eight provinces. The presence of DENV IgM and CHIKV IgM was examined by enzyme-linked immunosorbent assay. Of the 1306 sera tested, 210 were CHIKV seropositive and 82 were dengue seropositive. Statistical analysis demonstrated a significant increase in the CHIKV IgM antibody seropositivity rate in Kerman (OR = 2.07, 95% CI: 1.10-3.92; P = 0.024) and Fars (OR = 1.77, 95% CI: 1.06-2.93; P = 0.027). The DENV and CHIKV seropositivity rate in summer is higher than in other seasons (P < 0.01). Our seropositive samples suggest possible CHIKV and DENV infection in Iran. It is likely that these viruses are circulating in Iran and there is a need to study vector carriage of these two viruses.
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http://dx.doi.org/10.1017/S0950268820000114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7058646PMC
February 2020

Interleukin-1β and interleukin-6 in Common Variable Immunodeficiency and their association with subtypes of B cells and response to the Pneumovax-23 vaccine.

Eur Cytokine Netw 2019 Dec;30(4):123-129

Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran, Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Introduction: Common Variable Immunodeficiency (CVID) is the most common symptomatic form of primary immunodeficiencies. Current research data show altered B cells, TLRs, and cytokine profile in CVID patients. The aim of this study was to determine levels of IL-1β and IL-6 in CVID patients in response to TLRs stimulation and the association of these cytokines with subtypes of B cells and response to Pneumovax-23 vaccination.

Method: Peripheral blood mononuclear cells of CIVD patients were stimulated with and without TLR2 and TLR4 agonist and specific inhibitors including lipopolysaccharide (LPS), lipoteichoic (LTA), and OxPAPC. The levels of IL-1β and IL-6 were assessed by ELISA in different treatment groups. Finally, association of cytokines levels was assessed among different subtypes of B cells and types of response to Pneumovax-23 vaccine.

Results: Secretion of IL-6 and IL-1β was significantly diminished in CVID patients (p = 0.015 and p = 0.019), but ligand engagement of TLR2 and TLR4 leads to significant increase in IL-6 and IL-1β production. IL-6 was significantly lower in Pneumovax-23 hypo responder patients (p = 0.05) and significant correlations between the concentration of IL-6 and the number of switched memory and CD21 expressing B cells were found.

Conclusion: Secretion of IL-6 and IL-1β is abolished in CVID patients. However, TLR2 and TLR4 are hyper responsive to stimulation with their cognate ligands resulting in the secretion of higher levels of proinflammatory cytokines. This characteristic of CVID TLRs leads to an improvement of cytokine secretion compared to baseline levels. Also, our novel findings about the association concentrations of serum IL-6 and the frequency of with switched memory and CD21 expressing B cells as well as the poor response to Pneumovax-23 should be substantiated by the use of a higher sample size in future studies.
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http://dx.doi.org/10.1684/ecn.2019.0435DOI Listing
December 2019

Propidium monoazide-quantitative polymerase chain reaction (PMA-qPCR) assay for rapid detection of viable and viable but non-culturable (VBNC) in swimming pools.

J Environ Health Sci Eng 2019 Jun 7;17(1):407-416. Epub 2019 Mar 7.

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

Lack of culturability in the viable but non-culturable (VBNC) bacteria and the ability to regain infectivity in favourable conditions is one of the new challenges of public health providers for monitoring in environmental samples. Propidium monoazide quantitative polymerase chain reaction (PMA-qPCR) is one of the promising methods for timely detection of VBNC pathogens in environmental samples. We developed and used a method for the first time to detection of VBNC in swimming pool water samples using a membrane filter (MF). Moreover, the dominant model of the distribution of colonies on the MF and the effect of the culture medium and MF type on colony recovery by MF were evaluated. Swimming pool samples were subjected to conventional culture-based, qPCR and PMA-qPCR methods and the results were compared for the presence of VBNC in the samples. The positivity rate was 21% and 75% for in water samples as confirmed by standard culture-based and qPCR methods, respectively. Furthermore, of 24 samples, 9 (37.5%) were positive for VBNC . The developed qPCR/PMA-qPCR assay can detect the VBNC bacteria directly from aquatic samples and may result in better monitoring of recreational waters.
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http://dx.doi.org/10.1007/s40201-019-00359-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6582174PMC
June 2019

Association of polymorphisms in inflammatory cytokines encoding genes with severe cases of influenza A/H1N1 and B in an Iranian population.

Virol J 2019 06 13;16(1):79. Epub 2019 Jun 13.

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

Background: The increased levels of blood cytokines is the main immunopathological process that were attributed to severe clinical outcomes in cases of influenza A, influenza B and people with influenza-like illness (ILI). Functional genetic polymorphisms caused by single nucleotide polymorphisms (SNPs) in inflammatory cytokines genes can influence their functions either qualitatively or quantitatively, which is associated with the possibility of severe influenza infections. The aim of the present case-control study was to investigate the association of polymorphisms in inflammatory cytokines genes with influenza patients and ILI group in an Iranian population.

Methods: Total number of 30 influenza B, 50 influenza A (H1N1) and 96 ILI inpatient individuals were confirmed by Real-time RT-PCR and HI assays. The genotype determination was assessed for defined SNPs in IL-1β, IL-17, IL-10 and IL-28 genes.

Results: The frequencies of the IL-1β rs16944 (P = 0.007) and IL-17 rs2275913 (P = 0.006) genotypes were associated with severe influenza disease, while the frequencies of IL-10 rs1800872 and IL-28 rs8099917 were not associated with the disease (P > 0.05). Also, the absence of A allele in IL-17 rs2275913 SNP increased the risk of influenza A (H1N1) infection (P = 0.008).

Conclusions: This study demonstrated that influenza A- (H1N1) and B-infected patients and also ILI controls have different profiles of immune parameters, and individuals carrying the specific cytokine-derived polymorphisms may show different immune responses towards severe outcome.
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http://dx.doi.org/10.1186/s12985-019-1187-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6567579PMC
June 2019

Real-time polymerase chain reaction assays for rapid detection and virulence evaluation of the environmental Pseudomonas aeruginosa isolates.

Mol Biol Rep 2019 Aug 15;46(4):4049-4061. Epub 2019 May 15.

Center for Water Quality Research (CWQR), Institute for Environmental Research (IER), Tehran University of Medical Sciences, Tehran, Iran.

Rapid and species-specific detection, and virulence evaluation of opportunistic pathogens such as Pseudomonas aeruginosa, are issues that increasingly has attracted the attention of public health authorities. A set of primers and hydrolysis probe was designed based on one of the P. aeruginosa housekeeping genes, gyrB, and its specificity and sensitivity was evaluated by TaqMan qPCR methods. The end point PCR and SYBR Green qPCR were used as control methods. Furthermore, multiplex RT-qPCRs were developed for gyrB as reference and four virulence genes, including lasB, lasR, rhlR and toxA. Totally, 40 environmental samples, two clinical isolates from CF patients, two standard strains of P. aeruginosa, and 15 non-target reference strains were used to test the sensitivity and specificity of qPCR assays. In silico and in vitro cross-species testing confirmed the high specificity and low cross-species amplification of the designed gyrB418F/gyrB490R/gyrB444P. The sensitivity of both TaqMan and SYBR Green qPCRs was 100% for all target P. aeruginosa, and the detected count of bacteria was below ten genomic equivalents. The lowest M value obtained from gene-stability measurement was 0.19 that confirmed the suitability of gyrB as the reference gene for RT-qPCR. The developed qPCRs have enough detection power for identification of P. aeruginosa in environmental samples including clean and recreational water, treated and untreated sewage and soil. The short amplicon length of our designed primers and probes, alongside with a low M value, make it as a proper methodology for RT-qPCR in virulence genes expression assessment.
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http://dx.doi.org/10.1007/s11033-019-04855-yDOI Listing
August 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

Thymol as a reciprocal regulator of T cell differentiation: Promotion of regulatory T cells and suppression of Th1/Th17 cells.

Int Immunopharmacol 2019 Feb 31;67:417-426. Epub 2018 Dec 31.

Department of Immunology, Medical School, Shiraz University of Medical Sciences, Shiraz, Iran; Autoimmune Diseases Research Center, Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. Electronic address:

Regulatory T cells (Tregs) are critical for maintaining immune response and enhancing their differentiation has therapeutic implications for autoimmune diseases. In this study, we investigated the effects of thymol a well-known monoterpene from Thyme on differentiation and function of Tregs. In vitro generation of Tregs from purified naïve CD4CD25 T cells in the presence of thymol was carried out. Suppressor activity of generated Tregs was examined by changes in the proliferation of CFSE-labeled conventional T cells. Thymol promotes differentiation of naïve CD4CD25 T cells to CD4CD25Foxp3 Tregs [66.9-71.8% vs. control (47%)] and increased intensity of Foxp3 expression on Tregs (p < 0.01). In functional assay, an increased immune suppression by thymol-induced Tregs (≈2.5 times of untreated Tregs) was detected. For in vivo study, thymol was intraperitoneally administered to ovalbumin (Ova)-immunized mice. Flow cytometry assessment of spleens from thymol-treated Ova-immunized mice showed increased number of CD4 Foxp3 Tregs (>8%, p < 0.01(and decreased levels of CD4T-bet Th1 and CD4RORγt Th17 cells resulted in significant decreased Th1/Treg and Th17/Treg ratios. In ex vivo Ova challenge of splenocytes from thymol-treated Ova-immunized mice, similarly higher levels of CD4 Foxp3 Tregs, and also elevated TGF-β expression in CD4Foxp3 population (48.1% vs. 18.9% in untreated Ova-immunized group) and reduced IFN-γ-producing CD4T-bet T cells and IL-17-producing CD4RORγt T cells were detected. This led to marked decreased ratios of IFNγ/TGF-β and IL-17/TGF-β expressions. In conclusion, this study revealed thymol as a compound with enhancing effects on Treg differentiation and function, which may have potential benefits in treatment of immune-mediated diseases with Th1/Th17 over-activation.
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http://dx.doi.org/10.1016/j.intimp.2018.12.021DOI Listing
February 2019

Differential regulation of CD4 T cell subsets by Silymarin in vitro and in ovalbumin immunized mice.

Daru 2018 Dec 26;26(2):215-227. Epub 2018 Nov 26.

Department of Immunology, Medical School, Shiraz University of Medical Sciences, Shiraz, 71348-45794, Iran.

CD4 T cell subsets including regulatory T cells (Tregs), Th1 and Th17 are critical for control and development of inflammation and autoimmunity. We investigated the in vitro and in vivo effects of silymarin, a well-known herbal medicine on differentiation and function of Tregs and Th1 and Th17 responses. For in vitro study, mice splenocytes treated with 20-30 μg/ml silymarin were evaluated for gene expressions of specific transcription factors and cytokines of CD4 T cell subsets using real-time PCR. Induction of Treg cell development in the presence of silymarin was performed on isolated naïve CD4 T cells. Effect of silymarin-induced Tregs on T cell suppression was determined by CFSE labeling method. Results of this part showed that silymarin significantly decreased IFNγ, RORγt and IL-17 gene expressions and upregulated Foxp3, TGF-β and IL-10 mRNA. More silymarin-enhanced naïve CD4 T cells differentiated to Tregs (67%) than the control (47%). Silymarin-induced Tregs reduced proliferation of naïve activated T cells (<50%). For in vivo study, mice were immunized with ovalbumin (Ova) on days 1 and 14. Silymarin (100 mg/Kg) was intraperitoneally administered two days before the first Ova challenge followed by on every day for two weeks. Splenocytes were then isolated for assessment of CD4 T cell subsets and ex vivo analysis using flow cytometry. Treatment of Ova-immunized mice with silymarin increased Tregs (11.24 ± 1.2%, p < 0.01(but decreased Th1 (1.72 ± 0.4%, p < 0.001) and Th17 (1.07 ± 0.04%, p < 0.001) cells. Ex vivo Ova challenge of splenocytes from Ova-immunized mice treated with silymarin decreased proliferation of splenocytes, IFNγ (2.76% of control) and IL-17 (<8%) along with increased TGF-β (59.7%) expressions in CD4T-bet, CD4RORγt and CD4Foxp3 T cells, respectively. In conclusion, silymarin promoted Treg differentiation and function and decreased Th1 and Th17 cells. Silymarin may differentially regulate CD4 T cell responses which can provide potential benefits for its use as treatment of immune-related diseases. Graphical abstract ᅟ.
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http://dx.doi.org/10.1007/s40199-018-0229-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6279658PMC
December 2018

Influenza vaccine: Where are we and where do we go?

Rev Med Virol 2019 01 8;29(1):e2014. Epub 2018 Nov 8.

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

The alarming rise of morbidity and mortality caused by influenza pandemics and epidemics has drawn attention worldwide since the last few decades. This life-threatening problem necessitates the development of a safe and effective vaccine to protect against incoming pandemics. The currently available flu vaccines rely on inactivated viral particles, M2e-based vaccine, live attenuated influenza vaccine (LAIV) and virus like particle (VLP). While inactivated vaccines can only induce systemic humoral responses, LAIV and VLP vaccines stimulate both humoral and cellular immune responses. Yet, these vaccines have limited protection against newly emerging viral strains. These strains, however, can be targeted by universal vaccines consisting of conserved viral proteins such as M2e and capable of inducing cross-reactive immune response. The lack of viral genome in VLP and M2e-based vaccines addresses safety concern associated with existing attenuated vaccines. With the emergence of new recombinant viral strains each year, additional effort towards developing improved universal vaccine is warranted. Besides various types of vaccines, microRNA and exosome-based vaccines have been emerged as new types of influenza vaccines which are associated with new and effective properties. Hence, development of a new generation of vaccines could contribute to better treatment of influenza.
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http://dx.doi.org/10.1002/rmv.2014DOI Listing
January 2019

Molecular detection of HHV1-5, AAV and HPV in semen specimens and their impact on male fertility.

Hum Fertil (Camb) 2019 Jun 24;22(2):133-138. Epub 2018 Apr 24.

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

Viral infections have been considered as possible destructive factors that influence male fertility. The aim of this study was to determine the prevalence of human herpes viruses 1-5 (HHV1-5), adeno associated virus (AAV) and human papilloma virus (HPV) in semen and whether these influence semen quality. DNA extraction was performed using phenol-chloroform protocol, then three different nested-PCRs were done to detect HHV1-5, AAV and HPV DNAs in the semen samples. Of 145 samples, 66 (45.5%) were positive at least for one of the viruses. The genome detection rate of HSV1/2, VZV, EBV, HCMV, AAV and HPV were zero, 2.8%, zero, 1.4%, 27.6% and 19.3%, respectively. Of 66 positive samples for these viruses, 6 (4.1% of all samples) were positive for two viruses simultaneously. Here no association was found between variations in semen parameters related to fertility and detection of VZV, HCMV, AAV and HPV DNA in semen samples. It should be noted that the prevalence of different viruses in semen, and their relevance to male infertility, differs significantly due to the genome extraction and amplification methods or due to a real variation between study populations and geographical regions.
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http://dx.doi.org/10.1080/14647273.2018.1463570DOI Listing
June 2019

Spatial Distribution of Phlebotomine Sand Flies (Diptera: Psychodidae) as Phlebovirus Vectors in Different Areas of Iran.

J Med Entomol 2018 06;55(4):846-854

Department of Medical Entomology & Vector Control, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Sand fly fever is caused by Naples (SFNV) and Sicilian viruses (SFSV) and the closely related Toscana virus of the Phlebovirus genus in the family Bunyaviridae, and transmitted by Phlebotomine sand flies. Phlebotomus papatasi Scopoli, 1786 is known as the main vector of the disease. This study aimed to investigate the distribution of Phlebotomine sand flies as vector of sand fly fever viruses, and the effects of some environmental variables on their potential dispersion to new areas in some provinces of Iran. Sand flies were collected during their active season in the region using CDC light traps. Ecological parameters were recorded for each collection site. Arc GIS 10.3 software was used for data analysis and mapping the distribution of sand flies. Sampling in the study areas was carried out in six different climatic zones. Seventeen sand fly species were collected including eight species of genus Phlebotomus and nine species of genus Sergentomyia. The Medium Semi-Arid climatic zone had the highest species diversity. Fourteen species of sand flies were collected at altitude between 2 and 325 m, and seven species were collected between 326 and 1380 m above sea level. There was significant correlation between sand fly density and all tested environmental variables. Phlebotominae sand flies have wide distribution in Iran and have a major public health concern in the country. P. papatasi and Sergentomyia sintoni Pringle, 1933 prefers hot summers and rainfall. This poses a threat of transmission of sand fly fever caused by SFSV and SFNV across the country.
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http://dx.doi.org/10.1093/jme/tjy033DOI Listing
June 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

The Comparison of Sensitivity and Specificity of ELISA-based Microneutralization Test with Hemagglutination Inhibition Test to Evaluate Neutralizing Antibody against Influenza Virus (H1N1).

Iran J Public Health 2017 Dec;46(12):1690-1696

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

Background: The most common serological assay to measure anti-influenza antibodies is hemagglutination inhibition (HI) assay. Recently, neutralizing antibodies against influenza virus infection or vaccination can also be detected using microneutralization assays and occasionally, have greater sensitivity than the standard HI assays. The study aimed to compare the sensitivity and specificity of ELISA-based microneutralization (microNT-ELISA) and conventional HI assays in order to detect influenza H1N1 virus antibodies.

Methods: MicroNT-ELISA was set up according to the WHO Manual on Influenza Diagnosis and Surveillance in Virology Department of Tehran University of Medical Sciences for the detection of neutralizing antibodies against H1N1 influenza virus in 2013. Fifty serum samples were analyzed with both HI and microNT-ELISA assays. Correlation between methods was calculated by linear regression analysis.

Results: The linear correlation coefficient squares, R2, of microNT-ELISA and HI test was 0.61 (<0.0001) and we observed a high index of coincidence between the two tests. According to McNemar's test, there was no statistically significant difference between these two assays (>0.05).

Conclusion: The sensitivity and specificity of microNT-ELISA assay were high (87% and 73%, respectively) and closely related to gold standard test results. Therefore, microNT-ELISA is recommended as an alternative or complementary test to conventional HI assay for serological and epidemiological purposes.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5734969PMC
December 2017

Evaluation of Antibody and Cytokines Responses in Intranasally and Intramuscularly Administrated BALB/C Mice With Influenza Virus-Like Particle.

Acta Med Iran 2017 Oct;55(10):604-611

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

We previously developed an influenza virus like particle with HA, M, and NA proteins using Bac-to-Bac expression system and SF9 cell line. To evaluate the immunogenicity of our construct, we assessed the humoral, cytokine induced by H1N1-VLP in BALB/c mice immunized intranasally and intramuscularly. Enzyme-linked immunosorbent assay and Relative quantitative real-time PCR were used to evaluate the antibody (IgG and IgA) and mRNA levels of IL-6, IL-4, IL-10 and IFN-g in PBMCs. Our results showed that VLP was capable of intranasal (I.N.) and intramuscular (I.M.) induction of serum IgG and IgA responses. Interestingly, I.N. route induced higher IgG and IgA titer than I.M. route, which was statistically significant. Moreover, mRNA levels of IL-6 (4.2-4.5 folds), IFN-g (5.5-5.7 folds), and the anti-inflammatory cytokine IL-10 (2.5-3 folds) and IL-4 (2.4-2.8 folds) were significantly elevated in mice immunized I.N. and I.M. with H1N1-VLP compared to the control group. Our findings indicated that a non-infectious genome-less VLP approach mimics parenteral virus with multiple viral antigens and epitopes that stimulate a diverse set of immune responses such as innate immunity, specific serum IgG antibody, cell-mediated immunity, and local antibodies.
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October 2017

Effect of MicroRNA-21 Transfection on In-vitro Differentiation of Human Naive CD4+ T Cells to Regulatory T Cells.

Iran J Allergy Asthma Immunol 2017 Jun;16(3):235-244

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

Regulatory T cells (Tregs) are important components of the immune system that modulate responses of other cells. These cells are involved in peripheral tolerance mechanisms, so defect in development and function of these cells can result in autoimmune disease. Increasing evidence supports the role of microRNAs-21 (miR-21) in the regulation of forkhead box P3 (Foxp3) expression in Tregs. We aimed to determine whether miR-21 transfection to naive CD4+ T cells can be useful in generation of iTregs in-vitro. We investigated in-vitro differentiation of miR-21-transfected naive CD4+ T cells to iTregs and compared these iTregs to cytokine-differentiated iTregs and control group. We showed that expression of Foxp3, transforming growth factor beta (TGF-β), and interleukin-10 (IL-10) are increased in iTregs generated after miR-21 transfection in comparison with cytokine-differentiated iTregs and control group. Our findings demonstrate that miR-21 has positive role in in-vitro generation of induced regulatory T-cells (iTregs).
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June 2017

Evaluation of the expression level of 12/15 lipoxygenase and the related inflammatory factors (CCL5, CCL3) in respiratory syncytial virus infection in mice model.

Microb Pathog 2017 Aug 1;109:209-213. Epub 2017 Jun 1.

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

Human respiratory syncytial virus (RSV) is a leading cause of acute respiratory infection during early childhood and imposes a great burden on patients, parents, and society. Disease is thought to be caused, at least partially, by an excessive immune response. Pulmonary leukocyte infiltration is the result of a coordinated expression of diverse chemokines with distinct cellular specificities. Lipoxygenases (LOXs), as a key enzyme catalyzing deoxygenation of poly unsaturated fatty acids, regulate inflammation and have been suggested to play an important role in the immune response in viral infection. To expand our understanding on the possible role of LOX in respiratory viral infection, we studied the 12/15- lipoxygenase expression in RSV-related airway inflammation, and the related inflammatory chemokines, Chemokine (C-C motif) ligand 5 (CCL5) and Chemokine (C-C motif) ligand 3(CC L3) in both lung tissue and Bronchoalveolar lavage (BAL) fluid during experimental RSV infection. RSV infection induced mRNA expression of CCL5 and CCL3 in both BAL and lung tissue cells. In addition RSV infection enhanced expression of 12/15-LOX in both BAL and lung cells. In conclusion, we confirm that RSV infection leads to the increased expression of 12/15 LOX and the related chemokines CCL5 and CCL3 in BAL fluid and lung tissue cells suggesting that the 12/15 LOX pathway could serve as a candidate target for prevention and treatment of RSV infection.
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http://dx.doi.org/10.1016/j.micpath.2017.05.045DOI Listing
August 2017

The Effect of PTCC 1643 on Cultured Intestinal Epithelial Cells Infected with serovar Enteritidis.

Osong Public Health Res Perspect 2017 Feb 28;8(1):54-60. Epub 2017 Feb 28.

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

Objectives: Gastrointestinal disorders caused by serovar Enteritidis (sE) are a significant health problem around the globe. Probiotic bacteria have been shown to have positive effects on the immune responses. was examined for its capability to influence the innate immune response of HT29 intestinal epithelial cells towards sE. The purpose of this work was to assess the effect of PTCC 1643 on cultured intestinal epithelial cells infected with sE.

Methods: HT29 cells were cultured in Roswell Park Memorial Institute medium supplemented with 10% fetal bovine serum and 1% penicillin/streptomycin. The cells were treated with PTCC 1643 after or before challenge with sE. At 2 and 4 hours post-infection, we measured changes in the expression levels of and via real-time polymerase chain reaction.

Results: Treatment with inhibited sE-induced increases in and expression in the infected HT29 cells. Moreover, the expression of and in cells that were pretreated with and then infected with sE was significantly higher than that in cells infected with sE without pretreatment. Taken together, the results indicated that had an anti-inflammatory effect and modulated the innate immune response to sE by influencing and expression.

Conclusion: Our findings suggested that PTCC 1643 was able to suppress inflammation caused by sE infection in HT29 cells and reduce and expression. Additional in vivo and in vitro studies are required to further elucidate the mechanisms underlying this anti-inflammatory effect.
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http://dx.doi.org/10.24171/j.phrp.2017.8.1.07DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5402851PMC
February 2017

Seasonal influenza A/H3N2 virus infection and IL-1Β, IL-10, IL-17, and IL-28 polymorphisms in Iranian population.

J Med Virol 2016 12 27;88(12):2078-2084. Epub 2016 Jul 27.

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

Increased blood cytokines is the main immunopathological process that were attributed to severe clinical outcomes in cases of influenza A/H3N2 virus infection. The study was aimed to investigate the polymorphisms of IL-1β, IL-10, IL-17, and IL-28 genes to find the possibility of their association with the clinical outcome of influenza A/H3N2 virus infection among the infected patients in Iran. This is a Case-Control study in which influenza A/H3N2 virus positive confirmed with real-time PCR were the cases. DNA samples from groups were genotyped for polymorphisms in rs16944 (IL-1β), rs1800872 (IL-10), rs2275913 (IL-17), and rs8099917 (IL-28). Confidence interval (95%CI) and Odds ratio (OR) were calculated. IL-17 rs2275913 (GG and AG) were associated with risk of infection with that were statistically significant (P < 0.05, OR = 2.08-2.94). IL-1β (rs16944) (GG) was associated with reduced risk of infection (P < 0.01, OR = 0.46). Genotype GG and GT of IL-10 (rs1800872) were associated with increased risk of infection with influenza A/H3N2 virus (P < 0.05, OR = 2.04-2.58). In addition, IL-28 (rs8099917) genotypes GG (P < 0.05, OR = 0.49) and TG (P < 0.05, OR = 0.59) were associated with reduced risk of ILI symptom while genotype TT (P < 0.01, OR = 4.31) was associated with increased risk of ILI symptom. The results of this study demonstrated that polymorphisms of genes involved in the inflammatory and anti-inflammatory process affect the outcome of disease caused by influenza A/H3N2 virus. Thorough insight on host immune response at the time of influenza A virus infection is required to ensure adequate patient care in the case of feature outbreaks. J. Med. Virol. 88:2078-2084, 2016. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/jmv.24572DOI Listing
December 2016

Xenotropic Murine Leukemia Virus-Related Virus and RNase L R462Q Variants in Iranian Patients With Sporadic Prostate Cancer.

Iran Red Crescent Med J 2015 Dec 19;17(12):e19439. Epub 2015 Dec 19.

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

Background: Although several studies have confirmed the association of xenotropic murine leukemia virus-related virus (XMRV) and prostate cancer, this association is still controversial, as most studies did not detect XMRV in prostate tissue samples. Furthermore, some genetic and epidemiological studies have highlighted a role for RNase L polymorphisms, particularly R462Q, in the progression of prostate cancer.

Objectives: The focus of this study was on the association of XMRV and RNase L R462Q variants with the risk of prostate cancer in Iranian patients.

Patients And Methods: In this case-control study, 40 and 80 individuals with sporadic prostate cancer and benign prostatic hyperplasia, respectively, were included. The presence of XMRV was evaluated by real-time polymerase chain reaction (PCR) of integrase and nested-PCR for the gag genes. The RNase L R462Q polymorphism analysis was carried out by PCR and sequencing.

Results: In a total of 40 sporadic prostate cancer and 80 benign prostatic hyperplasia cases, no XMRV was detected by real-time PCR and nested-PCR. RNase L R462Q polymorphism analysis reveals that although there was an increase in the risk of prostate cancer correlated with the Q/Q allele of RNase L at position 462, the frequencies of the RNase L R462Q alleles were not statistically significant between the prostate cancer and benign prostatic hyperplasia groups (OR = 2.75 (95% CI = 0.67 - 11.3), P = 0.29).

Conclusions: These results did not support the presence of XMRV in the samples with prostate cancer and showed that RNase L R462Q variants had relatively little or no impact on the risk of prostate cancer in Iranian population.
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http://dx.doi.org/10.5812/ircmj.19439DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4700873PMC
December 2015

Prevalence and genotypic characterization of Human Parvovirus B19 in children with measles- and rubella-like illness in Iran.

J Med Virol 2016 Jun 13;88(6):947-53. Epub 2015 Nov 13.

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

Human Parvovirus B19 (B19V) is a prototype of the Erythroparvovirus genus in Parvoviridae family. B19V infections are often associated with fever and rash, and can be mistakenly reported as measles or rubella. Differential diagnosis of B19V illness is necessary for case management and also for public health control activities, particularly in outbreak situations in which measles or rubella is suspected. To investigate the causative role of B19V infection in children with measles- and rubella-like illness, a total of 583 sera from children with exanthema were tested for presence of B19V by determining anti-B19V IgG and IgM antibodies by ELISA as well as B19V DNA detection by nested PCR. DNA positive samples were assessed further for determination of viral load and sequence analysis by Real-Time PCR and Sanger sequencing method, respectively. Out of 583 patients, 112 (19.21%) patients were positive for B19V-IgM antibody, 110 (18.87%) were positive for B19V-IgG antibody, and 63 (10.81%) were positive for B19V viral DNA. The frequency of B19V-IgG antibodies were increased with age; that is children under 6 year old showed 7.11% seroprevalence for B19V-IgG as compared to 18.39% and 28.91% for age groups 6 to >11 and 11-14 years old, respectively. Phylogenetic analysis of the NS1-VPu1 overlapping region revealed that all sequenced B19V-DNA belonged to genotype 1. The results of this study may aid the surveillance programs aiming at eradicating measles/rubella virus in Iran, as infections with B19V can be mistakenly reported as measles or rubella if laboratory testing is not conducted.
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http://dx.doi.org/10.1002/jmv.24425DOI Listing
June 2016

A new insight into cancer stem cell markers: Could local and circulating cancer stem cell markers correlate in colorectal cancer?

Tumour Biol 2016 Feb 17;37(2):2405-14. Epub 2015 Sep 17.

Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran.

Cancer stem cell (CSC) markers could serve as potential prognostic procedure. This study is aimed to investigate the local expression of doublecortin-like kinase 1 (DCLK1) and Lgr5 in colorectal cancer tissues (CRC) at both protein and messenger RNA (mRNA) level, followed by providing a comparison of the local and circulating expression pattern of these markers, based on our present and previous study. The mRNA expression level of DCLK1 and Lgr5 was evaluated using comparative real-time PCR method applying 58 fresh tumor tissues and their correspondent normal margins. Immunohistochemistry was applied to analyze the protein expression level of DCLK1 and Lgr5 in paraffin-embedded CRC tissues. The correlation of DCLK1 and Lgr5 expression pattern with clinicopathological characteristics was assessed. A higher mRNA expression level of DCLK1 (3.28-fold change, p < 0.001) and Lgr5 (2.29-fold change, p < 0.001) was observed in CRC fresh tissues compared to the normal adjacent margins, and the expression level was higher in patients with higher grade and stages of disease and patients who underwent neoadjuvant chemoradiotherapy (CRT). The protein expression level of DCLK1 and Lgr5 was also increased significantly in tumor tissues compared to normal colon tissues which were positively correlated to tumor stage and grade and neoadjuvant CRT. Taken together, the results of protein analysis were in accordance with mRNA assessment. The local expression pattern of DCLK1 and Lgr5 was also in accordance with their expression level in circulation. However, some minor inconsistencies were observed which may be attributed to several factors including the possible effect of CRT on CSC reprogramming.
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http://dx.doi.org/10.1007/s13277-015-3989-7DOI Listing
February 2016

EBV and vitamin D status in relapsing-remitting multiple sclerosis patients with a unique cytokine signature.

Med Microbiol Immunol 2016 Apr 13;205(2):143-54. Epub 2015 Sep 13.

Virology Department, School of Public Health (SPH), Tehran University of Medical Sciences (TUMS), Tehran, 14155-6446, Iran.

Multiple sclerosis, a debilitating autoimmune and inflammatory disease of the central nervous system, is associated with both infectious and non-infectious factors. We investigated the role of EBV infection, vitamin D level, and cytokine signature in MS patients. Molecular and serological assays were used to investigate immune biomarkers, vitamin D level, and EBV status in 83 patients with relapsing-remitting multiple sclerosis and 62 healthy controls. In total, 98.8 % of MS patients showed a history of EBV exposure compared to 88.6 % in the healthy group (p = 0.005). EBV DNA load was significantly higher in MS patients than healthy subjects (p < 0.0001). Using a panel of biomarkers, we found a distinct transcriptional signature in MS patients compared to the healthy group with mRNA levels of CD73, IL-6, IL-23, IFN-γ, TNF-α, IL-15, IL-28, and IL-17 significantly elevated in MS patients (p < 0.0001). In contrast, the mRNA levels for TGF-β, IDO, S1PR1, IL-10, and CCL-3 were significantly lower in MS patients compared to healthy controls (p < 0.0001). No significant differences were found with the mRNA levels of IL-13, CCL-5, and FOXP3. Interestingly, in MS patients we found an inverse correlation between vitamin D concentration and EBV load, but not EBNA-1 IgG antibody levels. Our data highlight biomarker correlates in MS patients together with a complex interplay between EBV replication and vitamin D levels.
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http://dx.doi.org/10.1007/s00430-015-0437-7DOI Listing
April 2016

The TP53 Codon 72 Polymorphism and Risk of Sporadic Prostate Cancer among Iranian Patients.

Iran J Public Health 2014 Apr;43(4):453-9

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

Background: The TP53 gene is one of the most frequently mutated genes amongst human malignancies, particularly TP53 codon 72 polymorphism. Furthermore, an association between the TP53 codon 72 variants and prostate cancer has been reported in several studies. Although some studies have indicated an association between the TP53 Arg/Arg variant and an increased risk for prostate cancer, other studies have shown a positive correlation between the TP53 Pro/Pro genotype instead. Therefore, to clarify if this polymorphism is associated with an increased risk of prostate cancer in Iranian men, we conducted a case-control study of 40 sporadic prostate cancer patients and 80 benign prostate hyperplasia cases.

Methods: The TP53 codon 72 was genotyped using an allele specific PCR.

Results: A significant association between the TP53 codon 72 genotype and prostate cancer risk was found (OR = 6.8, 95% CI = [1.8-25.1], P = 0.005). However, the results of this study did not support an association between age, the Gleason score nor TP53 genotype at codon 72 in prostate cancer patients.

Conclusions: TP53 codon 72 polymorphism may have a great impact in the development of prostate cancer.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4433726PMC
April 2014

Intra-peritoneal and intra-rectal immunogenicity induced by rotavirus virus like particles 2/6/7 in mice.

Microb Pathog 2014 Feb-Mar;67-68:48-54. Epub 2014 Feb 28.

Virology Department, School of Public Health, Tehran University of Medical Sciences, 14155 Tehran, Iran; Virology Department, Pasteur Institute of Iran, Tehran, Iran. Electronic address:

We previously developed virus like particles of rotavirus (RV) with VP2, VP6, and VP7 proteins (VLP2/6/7) using stable High-five cell line. To evaluate the immunogenicity of our construct, we assessed the humoral and cytokine responses induced by VLP2/6/7 in BALB/c mice immunized intra-peritoneally and intra-rectally. Enzyme-linked immunosorbent assay (ELISA) and Relative quantitative (RQ) Real-time PCR were used to evaluate the antibody (IgG and IgA) levels in serum and mRNA levels of IL-6, IL-10 and IFN-γ in spleen cells, respectively. Our results showed that VLP2/6/7 is capable of intra-peritoneal (I.P.) and intra-rectal (I.R.) induction of serum IgG and IgA responses. IgA was detected in fecal samples of immunization groups by I.P. and I.R. routes. Interestingly, I.R. route induced higher IgA titer compared with I.P. route which was statistically significant. Moreover, mRNA levels of IL-6 and IFN-γ were significantly elevated in mice immunized intra-peritoneally with VLP2/6/7 compared to control group. As such, the mean change was 7.4 (P < 0.05) and 14.8 (P < 0.001) for IFN-γ and IL-6, respectively. Likewise, the same pattern was found when mice were immunized intra-rectally. Although elevated, the difference in the mean change for IL-10 was not statistically significant when compared to control group. Our findings indicated that VLPs constructed via a stable insect cell line are able to induce both humoral and cellular responses, a similar pattern as observed after immunization with live RVs.
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http://dx.doi.org/10.1016/j.micpath.2014.02.005DOI Listing
November 2014

Influenza Virus-like Particle Containing Two Different Subtypes of Hemagglutinin Confers Protection in Mice Against Lethal Challenge With A/PR8 (H1N1) and A/HK (H3N2) Viruses.

Iran Red Crescent Med J 2013 Jan 5;15(1):75-82. Epub 2013 Jan 5.

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

Background: Preventing the seasonal or pandemic outbreak of influenza can be powerful and cost-effective.

Objectives: In this study, we constructed a novel virus-like particle (VLP) platform that contains two hemagglutinin (HA) subtypes and evaluated immunogenicity of constructed VLP in mice.

Materials And Methods: This recombinant candidate vaccine model resulted in the expression of two HAs of H1N1 and H3N2 subtypes co-localized within a VLP. Following infection of insect cells with recombinant baculovirus co-expressing H1, H3 and M1 proteins, VLPs with size of 80-120 nm were self-assembled, budding, and released into the insect culture medium. The resulting VLPs which contained two different subtypes of hemagglutinin were purified by ultracentrifugation. The immunogenicity of VLPs was evaluated in mice following immunization.

Results: Our data showed that vaccination using VLPs elicited robust levels of serum IgG, and viral neutralizing antibodies against A/PR8 (H1N1) and A/HK (H3N2) viruses. Following challenge with lethal dose of A/PR8 (H1N1) and A/HK (H3N2, vaccinated mice were protected, displaying no sign of weight loss and mortality compared to non-vaccinated control mice.

Conclusions: VLPs can serve as a promising vaccination strategy to control influenza virus.
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http://dx.doi.org/10.5812/ircmj.6252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3589784PMC
January 2013