Publications by authors named "Zabihollah Shoja"

45 Publications

Severe acute respiratory syndrome-coronavirus-2 spike (S) protein based vaccine candidates: State of the art and future prospects.

Rev Med Virol 2020 Oct 15:e2183. Epub 2020 Oct 15.

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

Coronavirus disease 2019 (Covid-19) is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) which is responsible for a global pandemic that started in late 2019 in Wuhan, China. To prevent the worldwide spread of this highly pathogenic virus, development of an effective and safe vaccine is urgently needed. The SARS-CoV-2 and SARS-CoV share a high degree of genetic and pathologic identity and share safety and immune-enhancement concerns regarding vaccine development. Prior animal studies with first generation (whole virus-based) preparations of SARS-CoV vaccines (inactivated and attenuated vaccine modalities) indicated the possibility of increased infectivity or eosinophilic infiltration by immunization. Therefore, development of second and third generation safer vaccines (by using modern vaccine platforms) is actively sought for this viral infection. The spike (S) protein of SARS-CoVs is the main determinant of cell entry and tropism and is responsible for facilitating zoonosis into humans and sustained person-to-person transmission. Furthermore, 'S' protein contains multiple neutralizing epitopes that play an essential role in the induction of neutralizing antibodies (nAbs) and protective immunity. Moreover, T-cell responses against the SARS-CoV-2 'S' protein have also been characterized that correlate to the IgG and IgA antibody titres in Covid-19 patients. Thus, S protein is an obvious candidate antigen for inclusion into vaccine platforms against SARS-CoV-2 viral infection. This manuscript reviews different characteristics of S protein, its potency and 'state of the art' of the vaccine development strategies and platforms using this antigen, for construction of a safe and effective SARS-CoV-2 vaccine.
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http://dx.doi.org/10.1002/rmv.2183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646037PMC
October 2020

Combined use of lactic-acid-producing bacteria as probiotics and rotavirus vaccine candidates expressing virus-specific proteins.

Arch Virol 2021 Feb 3. Epub 2021 Feb 3.

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

Due to the lower efficacy of currently approved live attenuated rotavirus (RV) vaccines in developing countries, a new approach to the development of safe mucosally administered live bacterial vectors is being considered, using probiotic bacteria as an efficient delivery platform for heterologous RV antigens. Lactic acid bacteria (LAB), which are considered food-grade bacteria and normal microbiota, have been utilized throughout history as probiotics and developed since the 1990s as a delivery system for recombinant heterologous proteins. Over the last decade, LAB have frequently been used as a platform for the delivery of various RV antigens to the mucosa. Given the appropriate safety profile for neonates and providing the benefits of probiotics, recombinant LAB-based vaccines could potentially address the need for a subunit RV vaccine. The present review focuses mainly on different recombinant LAB vaccine constructs for RV and their potential as an alternative recombinant vaccine against RV disease.
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http://dx.doi.org/10.1007/s00705-021-04964-9DOI Listing
February 2021

Co-administration of 2'3'-cGAMP STING activator and CpG-C adjuvants with a mutated form of HPV 16 E7 protein leads to tumor growth inhibition in the mouse model.

Infect Agent Cancer 2021 Jan 26;16(1). Epub 2021 Jan 26.

Department of Virology, School of Public Health, Tehran University of Medical Sciences, 14155, Tehran, Iran.

Persistent infection with high-risk genotypes of human papillomavirus (HPV) is the leading cause of cervical cancer. The HPV oncoprotein E7 is constitutively expressed in cervical cancer and considered as an essential target for tumor-specific immunity. The goal of this study was to develop a candidate therapeutic vaccine based on the mutated E7 protein that had possibly reduced transformation capacity while was able to elicit a robust immune response. Therefore, the mutant type of HPV 16 E7 (E7GRG) protein was recombinantly expressed in E. coli. The protein was then purified and formulated with 2'-3'cGAMP CDN and/or CpG-C ODN adjuvants and subcutaneously injected to female C57BL/6 mice. To evaluate the immunogenic response, lymphocyte proliferation, secretion levels of IFN-γ and IL-4 cytokines, granzyme B level, and total IgG and subclasses of IgG antibody were measured. The anti-tumor activity was evaluated in tumor-harboring C57BL/6 mice. The highest rate of cell proliferation, IFN-γ and granzyme B levels, and amount of IgG antibody were found in mice group that were injected by E7GRG + 2'-3'cGAMP + CpG-C. Therapeutic immunization with E7GRG + 2'-3'cGAMP + CpG-C also significantly suppressed TC-1 tumor growth in mice. In conclusion, the results demonstrated that E7GRG + 2'-3'cGAMP + CpG-C induced strong cell-mediated and humoral immune responses that resulted in inhibition of tumor in mouse model.
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http://dx.doi.org/10.1186/s13027-021-00346-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836183PMC
January 2021

Association between circulating rotavirus genotypes and histo-blood group antigens in the children hospitalized with acute gastroenteritis in Iran.

J Med Virol 2021 Jan 19. Epub 2021 Jan 19.

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

Rotaviruses are the dominant cause of severe acute gastroenteritis in children under 5 years of age. Previous studies showed that some children are less susceptible to rotavirus gastroenteritis. It has been shown that this resistance depends on the rotavirus genotype and also human histo-blood group antigens (HBGAs), which works as a receptor for rotavirus surface protein (VP4). The present study aimed to evaluate the human genetic susceptibility to rotavirus gastroenteritis in Iran and to obtain a comparative analysis between rotavirus gastroenteritis and secretor or Lewis status in case and control groups in the Iranian population. The study was performed on fecal specimens from 108 children with acute rotavirus gastroenteritis from 2015 to 2017. A total of 50 fecal specimens from children with acute gastroenteritis of unknown etiology were also used as a control group. After the genotyping of positive rotavirus cases and human HBGAs by Sanger sequencing, the phylogenetic tree analysis showed that all rotavirus strains from Iran belonged to P[II]. The most common genotype was P[8] (n = 102; 94.4%), while the remaining belonged to P[4] (n = 3; 2.8%) and P[6] (n = 3; 2.8%) genotypes. The P[8] genotype was found to be associated with secretor and Lewis positive status (p < .05).
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http://dx.doi.org/10.1002/jmv.26808DOI Listing
January 2021

Lineage analysis of human papillomavirus types 31 and 45 in cervical samples of Iranian women.

J Med Virol 2020 Dec 28. Epub 2020 Dec 28.

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

Knowing the regional lineages/sublineages of human papillomavirus 31 (HPV 31) and 45 would be of great importance for further evolutionary, epidemiological, and biological analysis. In this regard, to characterize more common lineages and sublineages of HPV 31 and 45, the sequence variations of E6 gene were investigated in normal, premalignant, and malignant samples collected from the cervix in Iran. In total, 54 HPV 31- and 24 HPV 45-positive samples were analyzed by hemi-nested polymerase chain reaction (PCR) and nested-PCR, respectively. All PCR products were subjected to direct sequencing analysis. The results indicated that all three lineages A, B, and C were detected in HPV 31-positive samples; among which HPV 31 lineage A was dominant as it was found in 66.7% of all samples. HPV 31 lineages B and C were identified in 5.5% and 27.8% of samples, respectively. In HPV 45-infected samples, lineage B comprised of 62.5% of all samples and the remaining 37.5%  belonged to lineage A. In conclusion, our findings showed that lineage A of HPV 31 was predominant in Iran. Lineage B of HPV 45 was also dominant among Iranian women. However, further studies with larger sample size should be addressed to estimate the pathogenicity risk of HPV 31 or HPV 45 lineages/sublineages in the development of cervical cancer among Iranian women.
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http://dx.doi.org/10.1002/jmv.26748DOI Listing
December 2020

Estimation of genetic variation in the Secretor and Lewis genes in Iranian hospitalized children.

Transfus Clin Biol 2021 Feb 7;28(1):11-15. Epub 2020 Dec 7.

Department of Molecular Virology, Pasteur Institute of Iran, Tehran, Iran. Electronic address:

Background: The Secretor (FUT2) and lewis gene (FUT3) are in charge of the construction of histo-blood group antigens, which act as a receptor for some Pathogenes. This study aimed to estimate the prevalence of five significant single nucleotide polymorphisms (SNPs) in Iranian children.

Methods: In this cross-sectional study, 102 blood samples collected from hospitalized children. The FUT2 gene region was amplified and sequenced to explore rs1047781 and rs601338, and the FUT3 gene region was amplified to explore rs28362459, rs812936, rs778986 SNPs.

Results: In FUT2 gene, Se358,428 that produces Se phenotype with 63% (0.53 - 0.72) prevalence, was the most common genotype. For FUT3 gene Le59,202,314 with 80% prevalence was most common genotype (0.71 - 0.87).

Conclusion: This study genotyped Secretor and Lewis genes and designated SNPs' distinct distribution in Iran, and clarified at-risk groups for certain diseases.
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http://dx.doi.org/10.1016/j.tracli.2020.12.001DOI Listing
February 2021

Lineage analysis of human papillomavirus type 18 based on E6 region in cervical samples of Iranian women.

J Med Virol 2020 Jul 9. Epub 2020 Jul 9.

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

Distinct human papillomavirus (HPV) 18 variants are thought to differ in oncogenic potential and geographic distribution. As such, understanding the regional variants of HPV 18 would be of great importance for evolutionary, epidemiological, and biological analysis. In this regard, the sequence variations of E6 gene were investigated to characterize more common variants of HPV 18 in normal cells, premalignant, and malignant samples collected from the cervix. In total, 99 samples of HPV 18 were analyzed by polymerase chain reaction and sequencing. In overall, lineages A was identified in all study subjects, among which sublineage A4 was dominant although the difference observed was not statistically significant with regard to different stages of disease. Sublineage A4 comprised 90.9% of samples and the remaining were belonged to sublineages A1, A2, A3, and A5 at the frequency of 6.1%, 1%, 1%, and 1%, respectively. In conclusion, our findings clearly highlight the sublineage A4 of HPV 18 as the most dominant variant in Iran.
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http://dx.doi.org/10.1002/jmv.26283DOI Listing
July 2020

VP7 and VP4 genotypes of rotaviruses cocirculating in Iran, 2015 to 2017: Comparison with cogent sequences of Rotarix and RotaTeq vaccine strains before their use for universal mass vaccination.

J Med Virol 2020 08 9;92(8):1110-1123. Epub 2019 Dec 9.

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

The present study was conducted to analyze the genotypic diversity of circulating species A rotavirus (RVA) strains in Iran and also to investigate comparative analysis between the genotypes of VP4 and VP7 of cocirculating RVA and vaccine strains before the vaccine is introduced in the national immunization program. The G3-lineage I was found in this study as the most common G genotype which was followed by G9-lineage III, G1-lineages I, II, G12-lineage III, G2-lineage IV, and G4-lineage I. Also, P[8]-lineages III, IV was found as the predominant P genotype which was followed by P[4]-lineage V, and P[6]-lineage I. Overally, G3P[8] was determined as the most common combination. Moreover, the analysis of the VP7 antigenic epitopes showed that several amino acid differences existed between circulating Iranian and the vaccine strains. The comparison of genotype G1 of Iranian and vaccine strains (RotaTeq and Rotarix), and genotypes G2, G3, and G4 of Iranian and RotaTeq vaccine strains revealed three to five amino acids differences on the VP7 antigenic epitopes. Furthermore, analyzing of the VP8* epitopes of Iranian P[8] strains indicated that they contained up to 11 and 14 amino acid differences with Rotarix and RotaTeq, respectively. Based on different patterns of amino acid substitutions in circulating and vaccine strains, the emergence of antibody escaping mutants and potentially the decrease of immune protection might ensue in vaccinated children. However, considering the broad cross-protective activity of RVA vaccines, their efficacy should be monitored after the introduction in Iran.
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http://dx.doi.org/10.1002/jmv.25642DOI Listing
August 2020

A Meta-Analysis on Human Papillomavirus Type Distribution among Women with Cervical Neoplasia in the WHO Eastern Mediterranean Region.

Intervirology 2019 17;62(3-4):101-111. Epub 2019 Sep 17.

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

Introduction: To date, the human papillomavirus (HPV) vaccine has not been integrated into the national vaccination program of most countries of the WHO Eastern Mediterranean Region (EMRO), except for the United Arab Emirates and Libya. The knowledge of HPV genotype distribution in cervical neoplasia is valuable to predict the impact of current HPV vaccines on cancer prevention and can help the health policymakers to select the most appropriate vaccine types in their countries.

Methods: Hence, this meta-analysis recapitulates all available data on HPV prevalence and genotypes in women with atypical squamous cells of undetermined significance (ASCUS), cervical intraepithelial neoplasia (CIN) I-III or low- and high-grade squamous intraepithelial lesions (LSIL and HSIL, respectively), and invasive cervical cancer (ICC) in EMRO countries.

Results: The meta-analysis included 5,990 cases of cervical precancer and cancer. The overall HPV prevalence was 85.4, 71.3, 59.2, and 34.8% in women with ICC, CIN II-III or HSIL, CIN I or LSIL, and ASCUS, respectively. HPV 16 was the most common genotype followed by HPV 18, representing 58 and 16.5% in ICC cases, respectively.

Conclusion: This meta-analysis showed that the introduction of current HPV vaccines into national vaccination programs and the establishment of comprehensive screening programs in EMRO countries is beneficial by preventing 74.5% of cervical neoplasia.
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http://dx.doi.org/10.1159/000502824DOI Listing
January 2020

Epstein-Barr virus and risk of breast cancer: a systematic review and meta-analysis.

Future Oncol 2019 Aug 25;15(24):2873-2885. Epub 2019 Jul 25.

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

Despite the numerous publications regarding the role of Epstein-Barr virus (EBV) in breast cancer development, the topic has still remained controversial. The aim of the meta-analysis was to estimate the overall prevalence of EBV in the breast cancer population, and to investigate the association between EBV and breast cancer risk. The overall prevalence of EBV was calculated 26.37% (95% CI: 22-31%) from the 44 included studies. Meta-analysis of 30 case-control studies showed that the pooled association between EBV and risk of breast cancer is odds ratio 4.74 (95% CI: 2.92-7.69; Z = 6.30; p < 0.0001). Our analyses indicate a strong statistical relationship between EBV infection and risk of breast cancer, suggesting a potential role of EBV infection in the development of breast cancer.
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http://dx.doi.org/10.2217/fon-2019-0232DOI Listing
August 2019

Molecular analysis of human adenoviruses in hospitalized children <5 years old with acute gastroenteritis in Tehran, Iran.

J Med Virol 2019 11 18;91(11):1930-1936. Epub 2019 Jul 18.

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

Human adenoviruses (HAdVs), especially AdV-40 and 41, are common causes of nonbacterial sporadic and outbreak gastroenteritis in children. The present study aimed to describe the frequency and genetic analysis of HAdVs in hospitalized children <5 years old with acute gastroenteritis. A total of 376 stool samples obtained from June 2015 to December 2017 were investigated for the presence of HAdVs by polymerase chain reaction. The HAdV DNA was detected in 16 (4.3%) out of 376 stool samples. Based on the hexon hypervariable region (HVR), B, C, and F HADV species including five types HAdV-1, 2, 3, 6, and 41 were identified, among which enteric AdV species F (EAdV-41) was the most dominant. Moreover, our findings showed the presence of genomic type cluster 1 (GTC1) pattern in Iranian type 41 strains, which was closely similar to the D1 prototype strain (Tak) and D28. In this regard, a recombination was found in AdV-41 strains presenting the hexon sequence that belonged to GTC1, while fiber sequence clustered with GTC2.
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http://dx.doi.org/10.1002/jmv.25539DOI Listing
November 2019

Role of iron in cancer development by viruses.

Rev Med Virol 2019 07 17;29(4):e2045. Epub 2019 Apr 17.

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

Increased levels of iron in body are attributed to higher cancer risk. Given the fact that 16% of all human cancers are caused by viral infections, iron is suggested to play an important role in carcinogenesis particularly those induced by viral infections. The present study provides an updated summary of the literature and the plausible mechanisms of iron involvement in cancer development by viruses. Our understanding about the interplay between viral infections and iron in different settings particularly cancer development is yet to be improved as it may shed a new light in development of new therapeutic strategies.
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http://dx.doi.org/10.1002/rmv.2045DOI Listing
July 2019

Rotavirus VP6 as a potential vaccine candidate.

Rev Med Virol 2019 03 6;29(2):e2027. Epub 2019 Jan 6.

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

By the age of 5 years, virtually all children have been infected by group A rotavirus (RVA), which is responsible for around half million mortality annually prior to vaccination. Relatively high rate of the morbidity and mortality highlights the necessity of applying preventive procedures particularly in developing countries. Two live attenuated RVA vaccines (Rotarix and RotaTeq) are licensed and now being used in many countries worldwide. Although these vaccines are shown to reduce the mortality up to 50%, several key questions yet remained to answer. Indeed, the licensed RV vaccines were found to be less effective in countries of sub-Saharan Africa and Southeast Asia. Therefore, developing next generation RVA vaccines is warranted. VP6 is highly abundant and conserved protein that forms the middle layer of RV particles and was shown to be both antigenic and immunogenic. Although it does not induce neutralizing antibodies, different VP6 preparations were found to induce homologous and cross-reactive immune responses with partial protection from RVA replication. Although the molecular mechanisms are not fully elucidated, VP6-based RVA vaccine candidates are worthy of further consideration. This review aims to focus on different aspects of VP6 protein and its potentiality for an alternative RV vaccine against RV disease.
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http://dx.doi.org/10.1002/rmv.2027DOI Listing
March 2019

Human herpesvirus 8 DNA detection and variant analysis in patients with multiple sclerosis.

Virusdisease 2018 Dec 10;29(4):540-543. Epub 2018 Aug 10.

1Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, 14155 Iran.

Several studies reported a complex interplay between viral infections and neural cells leading to multiple sclerosis. A role for some viral infections has been proposed in MS. In this study, DNA sequences of human herpesvirus 8 (HHV-8) were searched in the peripheral blood of 54 patients with multiple sclerosis and 130 healthy subjects using nested-PCR assay to amplify ORF26 locus. Furthermore, HHV-8 positive samples were subjected to a nested-PCR to amplify K1 gene of HHV-8 followed by direct nucleotide sequencing. HHV-8 genome was detected in 18.5% (10/54) and 3% (4/130) of MS patients and controls, respectively, and the difference reached statistically significant level ( = 0.0017). Genotyping analysis revealed that genotype C was common (88.9%) in all study subjects, followed by genotype A. Our results showed higher detection of HHV-8 DNA in MS patients than control group.
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http://dx.doi.org/10.1007/s13337-018-0481-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6261899PMC
December 2018

Prevalence and genetic diversity of norovirus genogroup II in children less than 5 years of age with acute gastroenteritis in Tehran, Iran.

Med Microbiol Immunol 2018 Aug 4;207(3-4):201-210. Epub 2018 Apr 4.

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

Viral gastroenteritis is a major public health problem worldwide. In Iran, very limited studies have been performed with regard to the epidemiology of noroviruses. This study aimed to evaluate the prevalence and molecular epidemiology of GII noroviruses in hospitalized children less than 5 years of age with acute gastroenteritis (AGE). A total of 210 stool specimens were collected from Ali Asghar Children's Hospital and Bahrami Children's Hospital in Tehran, from June 2015 to June 2016. The samples were screened by real-time RT-PCR for genogroup II (GII). Positive samples were genotyped by semi-nested PCR followed by Sanger sequencing and phylogenetic analysis. Norovirus was identified in 36 (17.1%) of 210 specimens. Based on genetic analysis of RdRp and capsid sequences, the strains were clustered into eight RdRp-capsid genotypes: GII.P4-GII.4 Sydney_2012 (41.7%), GII.Pe-GII.4 Sydney_2012 (30.6%), GII.P21-GII.3 (13.9%), GII.P16-GII.4 Sydney_2012 (2.8%), GII.P16-GII.12 (2.8%), GII.P2-GII.4 Sydney_2012 (2.8%), GII.P7-GII.7 (2.8%) and GII.P2-GII.2 (2.8%). We determined several different co-circulating norovirus genotypes in children < 5 years of age with AGE in our hospital in Tehran, Iran. Continued molecular surveillance of noroviruses, including typing of both RdRp and capsid genes, is important for monitoring emerging strains in our continued efforts to reduce the overall burden of norovirus disease.
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http://dx.doi.org/10.1007/s00430-018-0541-6DOI Listing
August 2018

Type-Specific Human Papillomavirus Prevalence in Iranian Women with Normal Cervical Cytology: The Impact of Current HPV Vaccines.

Intervirology 2017 25;60(4):125-130. Epub 2018 Jan 25.

Objective: Human papillomavirus (HPV) vaccination is currently not included in the national vaccination program in Iran. Regional data on the distribution of HPV types in women are important as they can predict the impact of currently available vaccines and help health policy makers to consider all the possibilities with regard to HPV vaccination.

Methods: A total of 1,218 Iranian women with normal cervical cytology were included in this study. The presence of the HPV genome was investigated in all specimens by PCR assay, and all HPV-positive samples were genotyped.

Results: Totally, HPV was detected in 88 samples (7.2%). According to different geographical regions, the HPV prevalence varied: the highest HPV prevalence was observed in the North (11.7%) and the lowest in the Center (4.5%) of Iran, and this difference reached a statistically significant level (p < 0.05). In this study, the most frequent HPV types were HPV 16, 18, 66, and 11, representing 63.8% of all HPV infections.

Conclusion: Based on this study, it is estimated that HPV vaccines could have a great impact on the prevention of cervical cancer in Iran. This study highlights the necessity of introducing educational programs in high schools, robust screening programs, and vaccination in Iran.
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http://dx.doi.org/10.1159/000485898DOI Listing
August 2018

Immunization of Mice by Rotavirus NSP4-VP6 Fusion Protein Elicited Stronger Responses Compared to VP6 Alone.

Viral Immunol 2018 04 29;31(3):233-241. Epub 2017 Nov 29.

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

Due to the limitations and safety issues of the two currently approved live attenuated rotavirus (RV) vaccines "RotaTeq and Rotarix," studies on nonreplicating sources of RV vaccines and search for proper RV antigens are actively carried out. The adjuvant activity of NSP4 and highly immunogenic properties of RV VP6 protein prompted us to consider the construction of a NSP4-VP6 fusion protein and to assess the anti-VP6 IgG, IgA, and IgG subclass responses induced by Escherichia coli-derived NSP4-VP6 fusion protein compared to that of VP6 protein with/without formulation in Montanide ISA 50V2 (M50) in BALB/c mice. Results indicated to the proper expression of the fused NSP4-VP6 and VP6 proteins in E. coli. Intraperitoneal immunization by M50 formulated NSP4-VP6 fusion protein (M5+NSP4-VP6) induced the highest titration of VP6-specific IgG and IgA responses compared to the other groups. Indeed, the presence of NSP4 resulted to the induction of stronger humoral immune responses against the fused protein compared to that elicited by administration of VP6 protein alone (with/without M50 formulation), implying the adjuvant properties of NSP4 for the fused protein. Moreover, the "M50+NSP4-VP6" formulation induced higher serum IgG2a titers than IgG1 and increased Interferon-γ levels, despite unchanged interleukin-4 amounts compared to other groups, indicating Th1-oriented responses with a possible role of NSP4. In conclusion, this study further highlights the potentiality of NSP4-VP6 fusion protein as an efficient and cost-effective immunogen in the field of RV vaccine development.
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http://dx.doi.org/10.1089/vim.2017.0075DOI Listing
April 2018

Human papillomavirus type 16 lineage analysis based on E6 region in cervical samples of Iranian women.

Infect Genet Evol 2017 11 25;55:26-30. Epub 2017 Aug 25.

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

It is suggested that distinct HPV 16 variants differ in oncogenic potential and geographic distribution. As such, understanding the regional variants of HPV 16 would be of great importance for evolutionary, epidemiological and biological analysis. In this regard, the sequence variations of E6 gene were investigated to characterize more common variants of HPV 16 in normal cells, premalignant and malignant lesions of the cervix. In total, 106 isolates of HPV 16 were analyzed by PCR and sequencing. Overall, two different lineages (A and D) were identified. Lineage D comprised 70.7% of samples and the remaining 29.3% belonged to lineage A. Regarding to cytology/histology, lineage D was dominant in both normal+CIN I-II and CIN III+ICC groups as it was detected in 80% and 66.2% of cases, respectively. The comparison of the lineages between different groups (35 normal+CIN I-II samples and 71 CIN III+ICC samples) revealed that lineage A is more prevalent in cervical cancer cases (7 (20%) vs. 24 (33.8%)) although the difference observed did not reach statistical significance (p=0.07). In conclusion, our findings confirm that HPV lineages A and D are more prevalent in Iran, with the lineage D as the most dominant in all studied groups.
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http://dx.doi.org/10.1016/j.meegid.2017.08.025DOI Listing
November 2017

Type-specific human papillomavirus prevalence in cervical intraepithelial neoplasia and cancer in Iran.

J Med Virol 2018 01 6;90(1):172-176. Epub 2017 Oct 6.

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

In Iran, human papillomavirus (HPV) vaccination is not currently included in the national vaccination program and there are no comprehensive approaches to cervical screening program. Regional data on distribution of HPV types in women is important to predict the impact of current HPV vaccines. Although several studies on distribution of HPV types in cervical precancer and cancer have been conducted in Iran, in most of them HPV positive samples were subjected to specific-primer genotyping (mainly 16 and 18), and leaving the other HPV genotypes almost undetermined. Therefore, the present study aimed to investigate the distribution of HPV types in cervical neoplasia from West and Northwest of Iran. A total of 112 women with atypia, cervical intraepithelial neoplasia, and invasive cervical cancer were included. A PCR assay was performed in all samples to detect the presence of the HPV genome using the GP5+/6+ L1 consensus primer set. All HPV positive samples were subjected for sequencing. In overall, HPV prevalence was 20% in atypica, 44.5% in cervical intraepithelial neoplasia I, 92.3% in cervical intraepithelial neoplasia II-III, and 98.2% in invasive cervical cancer. The most frequent HPV type was HPV 16 (79.2%), which was followed by HPV types 18, 6, and 33 at the frequencies of 6.5%, 5.1%, and 2.7%, respectively. The least HPV types were found to be 31, 45, 53, 58, and 66. In conclusion, this study shows that the current HPV vaccines could have great impact to reduce the burden of cervical cancer in Iran.
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http://dx.doi.org/10.1002/jmv.24908DOI Listing
January 2018

Human herpes virus 6 status in relapsing-remitting multiple sclerosis patients.

Intern Med J 2017 Mar;47(3):339-341

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

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http://dx.doi.org/10.1111/imj.13363DOI Listing
March 2017

Multiple sclerosis-associated retrovirus, Epstein-Barr virus, and vitamin D status in patients with relapsing remitting multiple sclerosis.

J Med Virol 2017 07 8;89(7):1309-1313. Epub 2017 Mar 8.

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

The relationship between infections and autoimmune diseases is complex and there are several reports highlighting the role of human endogenous retroviruses (HERVs) in these patients. The levels of multiple sclerosis-associated retrovirus (MSRV)-type DNA of Env gene was measured in peripheral blood mononuclear cells from 52 patients with relapsing-remitting multiple sclerosis (RRMS) and 40 healthy controls using specific quantitative PCR (qPCR) analysis. Furthermore, we analyzed the status of HERV-W/MSRV in these patients with regards to both EBV (DNA load and anti-EBNA1 IgG antibody) and vitamin D concentration. MSRV DNA copy number were significantly higher in RRMS patients than healthy controls (P < 0.0001). Interestingly, an inverse correlation was found between MSRV DNA copy number and serum vitamin D concentration (P < 0.01), but not for EBV load or anti-EBNA-1 IgG antibody.
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http://dx.doi.org/10.1002/jmv.24774DOI Listing
July 2017

MDM2 gene polymorphisms and risk of classic Kaposi's sarcoma among Iranian patients.

Med Microbiol Immunol 2017 Apr 12;206(2):157-163. Epub 2017 Jan 12.

Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, 14155, Iran.

A single-nucleotide polymorphism (SNP) in the promoter region of MDM2 (SNP309T>G, rs2279744) has been shown to increase the expression of the MDM2 protein in various cancer types. However, only one study has analyzed the role of the MDM2 polymorphism in the development of Kaposi's sarcoma (KS). The association of MDM2 SNP309 with classic KS risk was evaluated in 79 Iranian patients with classic KS and 123 healthy controls. The MDM2 SNP309 was genotyped using PCR and restriction fragment length polymorphism methods. No significant correlation was found between the SNP309 polymorphism in MDM2 promoter and classic KS risk. There was no significant correlation between gender and disease stage. However, a significant association was found between SNP309 GG genotype and younger age (≤50 years) (odds ratio 9.5, 95% confidence intervals 1.5-60, p = 0.03). Our findings support no major role for the MDM2 SNP309 in KS development although it might influence the clinical outcome of KS in younger patients.
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http://dx.doi.org/10.1007/s00430-016-0491-9DOI Listing
April 2017

Molecular typing of human herpesvirus 8 among HIV positive in comparison to HIV-negative individuals in Iran.

J Med Virol 2017 04 26;89(4):703-709. Epub 2016 Dec 26.

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

It is still unclear whether different HHV-8 genotypes may have different pathogenic and tumorigenic properties associated with a diverse rate of disease progression. In some areas where genotype C was found to be prominent among classic KS patients, genotype A was shown to be more frequent among AIDS-associated KS patients. Genotype C was previously reported to be widespread in Iran, with genotype A being less frequent among patients with classic KS although no data are available with regards to the HHV-8 genotyping among Iranian HIV-infected patients. In order to analyze HHV-8 genotypes (ORF K1), six HIV-infected patients (with or without KS), and 22 HIV-negative subjects (classic/iatrogenic KS patients and IVDUs) were investigated using nested PCR. Genotype A was detected more frequently among HIV-infected patients with or without KS (three out of six) whereas genotype C was found more common among HIV-negative subjects including classic/iatrogenic KS patients and IVDSs (21 out of 22), and this difference was statistically significant (P = 0.044). In conclusion, our data further support the dominancy of HHV-8 genotype C in Iranian general population. Moreover, genotype A was more common among HIV-infected patients with or without KS. J. Med. Virol. 89:703-709, 2017. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/jmv.24644DOI Listing
April 2017

The Effect of Different microRNA Backbones on Artificial miRNA Expression and Knockdown Activity Against HIV-1 Replication.

Microrna 2016 ;5(2):146-151

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

Background: Artificial microRNAs (miRNAs) are designed to develop an RNAi-based gene therapy. Recently, it has been suggested that the flanking sequences and terminal loop structure play a critical role in RNAi biogenesis and target recognition, but no extensive study regarding the different miRNA backbone for artificial miRNAs optimization has been conducted.

Objective: We tested three artificial miRNAs with human hsa-miR30a (common miRNA), hsa-miR150 (T cell specific miRNA), and hsa-miR122 (liver specific miRNA) backbones in HEK-293T and Jurkat cell lines.

Methods: Artificial miRNA processing and knockdown efficiency were analyzed by stem-loop RT-PCR, qRT-PCR, luciferase assay and target challenging.

Results: We identified strikingly different RNAi activities among these different artificial miRNAs. Our results demonstrated that expression and function of art-miR150 was more than art-miR30 and artmiR122 in both HEK-293T and Jurkat cell lines. Since the main difference in these artificial miRNAs was flanking sequences and terminal loop structure, the change between the expression and function of artificial miRNAs can be attributed to these structures.

Conclusion: This study showed that expression of cell-specific artificial miRNA in target and nontarget cells is not different, but variation in flanking sequences and terminal loop can be involved in expression and function of artificial miRNAs. These results can be important for improving artificial miRNA design in RNAi-based gene therapy.
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http://dx.doi.org/10.2174/2211536605666160708235058DOI Listing
July 2017

Efficient inhibition of human immunodeficiency virus replication using novel modified microRNA-30a targeting 3'-untranslated region transcripts.

Exp Ther Med 2016 May 2;11(5):1833-1838. Epub 2016 Mar 2.

Virology Department, School of Public Health, Tehran University of Medical Sciences, Tehran 14716-13151, Iran.

RNA interference (RNAi)-based gene therapy is currently considered to be a combinatorial anti-human immunodeficiency virus-1 (HIV-1) therapy. Although artificial polycistronic microRNAs (miRs) can reduce HIV-1 escape mutant variants, this approach may increase the risk of side effects. The present study aimed to optimize the efficiency of anti-HIV RNAi gene therapy in order to reduce the cell toxicity induced by multi-short hairpin RNA expression. An artificial miR-30a-3'-untranslated region (miR-3-UTR) obtained from a single RNA polymerase II was used to simultaneously target all viral transcripts. The results of the present study demonstrated that HIV-1 replication was significantly inhibited in the cells with the miR-3-UTR construct, suggesting that miR-3'-UTR may serve as a promising tool for RNAi-based gene therapy in the treatment of HIV-1.
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http://dx.doi.org/10.3892/etm.2016.3121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4840495PMC
May 2016

Quantitative Evaluation of BAFF, HMGB1, TLR 4 AND TLR 7 Expression in Patients with Relapsing Remitting Multiple Sclerosis.

Iran J Allergy Asthma Immunol 2016 Feb;15(1):75-81

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

Multiple sclerosis is a chronic inflammatory disease of the central nervous system characterized by a complex immune response. Because of the complex nature of MS pathogenesis, a panel of biomarkers derived from different platforms will be required to reflect disease-related alterations. Monitoring and evaluation of molecules associated with the pathogenesis of the disease would provide useful information on disease progression and therapeutic assessment. In view of this, we evaluated the mRNA expression levels of B-cell activating factor (BAFF), high mobility group box 1 (HMGB-1), Toll like receptor (TLR) 4 and TLR7 in MS. These molecules are implicated in the pathogenesis of MS; however, they havereceived little attention. PBMCs were isolated from whole blood of 84 Relapsing Remitting Multiple Sclerosis patients and 70 healthy controls. Relative quantitative RT-PCR was applied to quantify the transcriptional levels of the immune markers. The mRNA expression levels of TLR7 were significantly elevated in RRMS patients than healthy controls. Whereas, TLR4 expression was found to be significantly lower in the patients than control group. We found no difference analyzing the mRNA levels of BAFF and HMGB1. Our data highlights the immune marker correlates in RRMS patients. However, further in-depth studies are warranted to check for their reliability of biomarkers in autoimmune diseases such as MS.
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February 2016

Prevalence of human herpesvirus-8 among HIV-infected patients, intravenous drug users and the general population in Iran.

Sex Health 2016 06;13(3):295-8

Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran 14155, Iran.

Studies looking at the frequency of human herpesvirus-8 (HHV-8) among Iranian blood donors have produced conflicting results. The aim of this study was to investigate the prevalence of HHV-8 DNA by using polymerase chain reaction methods among 168 healthy individuals, 60 intravenous drug users and 100 HIV-infected patients from Iran. The prevalence of HHV-8 was significantly higher among intravenous drug users (13.3%) compared with the general population (3.6%; P=0.017). The HHV-8 genome was mostly detected among intravenous drug users who displayed high-risk sexual behaviours. Moreover, the HHV-8 genome was also detected in 8% of HIV-infected patients. The present study findings support the likelihood that the transmission of HHV-8 is via a sexual route in the Iranian population.
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http://dx.doi.org/10.1071/SH15192DOI Listing
June 2016

First report of human parvovirus 4 detection in Iran.

J Med Virol 2016 08 4;88(8):1314-8. Epub 2016 Feb 4.

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

Parvovirus 4 (PARV4) is an emerging and intriguing virus that currently received many attentions. High prevalence of PARV4 infection in high-risk groups such as HIV infected patients highlights the potential clinical outcomes that this virus might have. Molecular techniques were used to determine both the presence and the genotype of circulating PARV4 on previously collected serum samples from 133 HIV infected patients and 120 healthy blood donors. Nested PCR was applied to assess the presence of PARV4 DNA genome in both groups. PARV4 DNA was detected in 35.3% of HIV infected patients compared to 16.6% healthy donors. To genetically characterize the PARV4 genotype in these groups, positive samples were randomly selected and subjected for sequencing and phylogenetic analysis. All PARV4 sequences were found to be genotype 1 and clustered with the reference sequences of PARV4 genotype 1. J. Med. Virol. 88:1314-1318, 2016. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/jmv.24485DOI Listing
August 2016

The prevalence of human papillomavirus infection in Iranian patients with sinonasal inverted papilloma.

J Chin Med Assoc 2016 Mar 9;79(3):137-40. Epub 2016 Jan 9.

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

Background: Inverted papilloma (IP) is an uncommon disease which arises in the mucosal membrane of the nasal cavity and paranasal sinus. It has been proposed that human papillomavirus (HPV) is the causal agent in the pathogenesis of IP and plays a key role in the progression from benign IP to malignancy. As there are no prior studies that focus on an Iranian population, this study intended to characterize the prevalence of HPV types in benign and malignant forms of IP.

Methods: In this retrospective study, we included a total of 40 IP patients [37 benign IP and 3 IP/squamous cell carcinoma (SCC)] who were referred to Amiralam Hospital in Tehran from 2004-2006.

Results: HPV was detected in 18.9% and 100% of IP and IP/SCC cases, respectively. In all HPV positive cases of IP and IP/SCC cases, HPV6/11 and HPV16/18 were detected, respectively. Therefore, HPV types were different between the IP and IP/SCC patients, and this difference was statistically significant (p = 0.002).

Conclusion: This study suggests that HPV6 and 11 may be involved in the development of IP, but HPV16 and 18 likely play an important role in the progression from benign to malignant form of IP.
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http://dx.doi.org/10.1016/j.jcma.2015.11.003DOI Listing
March 2016

Diversity of VP7 genes of G1 rotaviruses isolated in Iran, 2009-2013.

Infect Genet Evol 2016 Jan 30;37:275-9. Epub 2015 Sep 30.

Virology Department, Pasteur Institute of Iran, Tehran, Iran. Electronic address:

Genotype G1 of rotaviruses (RVs) is the most prevalent strain in human RV infections around the world. The present study evaluated genetic variations in the VP7 gene of RV G1 genotype isolates from Iran. Genetic and phylogenetic analyses indicated that RV strains from Iran clustered with G1 lineages IA, IC, and IIC, showing highest average of similarity versus reference sequences of the G1 lineages I and II. This study highlights the genetic pattern of G1 RV on the basis of distinct lineages and sublineages and indicates the importance of continuous monitoring on genetic variation and evolution pattern of G1 RV strains across the Iranian population for the final aim of RV vaccine introduction.
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http://dx.doi.org/10.1016/j.meegid.2015.09.025DOI Listing
January 2016