Publications by authors named "Nastaran Khodadad"

9 Publications

  • Page 1 of 1

A knockdown of the herpes simplex virus type-1 gene in all-in-one CRISPR vectors.

Folia Histochem Cytobiol 2020 16;58(3):174-181. Epub 2020 Sep 16.

Fuller Laboratories, Fullerton, CA, USA.

Introduction: Herpes simplex virus type 1 (HSV-1) is a virus that causes serious human disease and establishes a long-term latent infection. The latent form of this virus has shown to be resistant to antiviral drugs. Clustered Regularly Interspace Short Palindromic Repeats (CRISPR), is an important tool in genome engineering and composed of guide RNA (gRNA) and Cas9 nuclease that makes an RNA-protein complex to digest exclusive target sequences implementation of gRNA. Moreover, CRISPR-Cas9 system effectively suppresses HSV-1 infection by knockout of some viral genes.

Materials And Methods: To survey the efficacy of Cas9 system on HSV-1 genome destruction, we designed several guide RNAs (gRNAs) that all packaged in one vector. Additionally, we performed a one-step restriction using BamHI and Esp3I enzymes.

Results: CRISPR/Cas9 system targeted against the gD gene of HSV-1 was transfected into HEK-AD cells that showed a significant reduction of HSV-1 infection by plaque assay and real-time PCR.

Conclusion: The pCas-Guide-EF1a-GFP CRISPR vector can create a fast and efficient method for gRNA cloning by restriction enzymes (Esp3I (BsmBI) and BamHI). Therefore, the CRISPR/Cas9 system may be utilized for the screening of genes critical for the HSV-1 infection and developing new strategies for targeted therapy of viral infections caused by HSV-1.
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http://dx.doi.org/10.5603/FHC.a2020.0020DOI Listing
September 2020

In silico functional and structural characterization of hepatitis B virus PreS/S-gene in Iranian patients infected with chronic hepatitis B virus genotype D.

Heliyon 2020 Jul 15;6(7):e04332. Epub 2020 Jul 15.

Infectious and Tropical Disease Research Center, Health Research Institute, and Department of Virology, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

Objective: Chronic hepatitis B (CHB) virus infection is the most prevalent chronic liver disease and has become a serious threat to human health. In this study, we attempted to specify and predict several properties including physicochemical, mutation sites, B-cell epitopes, phosphorylation sites, N-link, O-link glycosylation sites, and protein structures of S protein isolated from Ahvaz.

Materials And Methods: Initially, hepatitis B virus DNA ( DNA) was extracted from five sera samples of untreated chronic hepatitis B patients. The full-length genomes were amplified and then cloned in pTZ57 R/T vector. The full sequences of were registered in the GenBank with accessions numbers (MK355500), (MK355501) and (MK693107-9). PROTSCALE, Expasy's ProtParam, immuneepitope, ABCpred, BcePred, Bepipred, Algpred, VaxiJen, SCRATCH, DiANNA, plus a number of online analytical processing tools were used to analyse and predict the gene of genotype sequences. The present study is the first analytical research on samples obtained from Ahvaz.

Results: We found major hydrophilic region (MHR) mutations at "a" determining region that included and mutations. Moreover, Ahvaz sequences revealed four sites (4, 112, 166, and 309) in the gene for N-glycosylation that could possibly be a potential target for anti- therapy.

Conclusion: In the present study, mutations were identified at positions T113S and N131T within the MHR region of S protein; these mutations can potentially decrease the effect of hepatitis B vaccination in vaccine recipients.
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http://dx.doi.org/10.1016/j.heliyon.2020.e04332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7365991PMC
July 2020

The AP-1 pathway; A key regulator of cellular transformation modulated by oncogenic viruses.

Rev Med Virol 2020 01 1;30(1):e2088. Epub 2019 Dec 1.

Hepatitis Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran.

Cancer progression is critically associated with modulation of host cell signaling pathways. Activator protein-1 (AP-1) signaling is one such pathway whose deregulation renders the host more susceptible to cancer development. Oncogenic viruses, including hepatitis B virus, hepatitis C virus, human papilloma virus, Epstein-Barr virus, human T-cell lymphotropic virus type 1, and Kaposi's sarcoma-associated herpes virus, are common causes of cancer. This review discusses how these oncoviruses by acting through various aspects of the host cell signaling machinery such as the AP-1 pathway might affect oncoviral tumorigenesis, replication, and pathogenesis. The review also briefly considers how the pathway might be targeted during infections with these oncogenic viruses.
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http://dx.doi.org/10.1002/rmv.2088DOI Listing
January 2020

Molecular epidemiology of JC polyomavirus in HIV-infected patients and healthy individuals from Iran.

Braz J Microbiol 2020 Mar 30;51(1):37-43. Epub 2019 Jul 30.

Department of Virology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

JC polyomavirus (JCPyV) is the causative agent for progressive multifocal leukoencephalopathy (PML) in immunocompromised patients. More than 40% of healthy population excretes JCPyV particles in their urine. As JCPyV is ubiquitous in human, the definition of genotype distribution can help trace population migration. In this study, to define the frequency of JCPyV in southwest of Iran, urine samples of 161 volunteers including 80 healthy individuals and 81 HIV-infected patients were collected. PCR assays and sequence analysis were performed using JCPyV-specific primers designed against VP1 coding region. JCPyV DNA was detected in 65 out of 81 urine samples (80.2%) of HIV-infected, and in 43 out of 80 urine samples (53.8%) of healthy individuals (P = 0.001). The shedding of JCPyV among HIV-infected patients revealed an age-related pattern while such relationship was not observed in healthy individuals group. The most common genotype found in this region was genotype 3A (80.8%), followed by genotype 2D (11.5%), 4 (3.8%), and 7 (3.8%). The frequency of JCPyV in the urine of HIV-infected patients was found significantly higher than in the healthy individuals (P = 0.001).
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http://dx.doi.org/10.1007/s42770-019-00117-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7058753PMC
March 2020

Zinc Sulfate in Narrow Range as an In Vitro Anti-HSV-1 Assay.

Biol Trace Elem Res 2020 Feb 26;193(2):410-413. Epub 2019 Apr 26.

Department of Modern Sciences and Technologies, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

This report explains the employing of a combination test of traditional cell culture with a quantitative real-time PCR for assessment of the antiviral effect of zinc sulfate (ZnSO) on herpes simplex virus (HSV)-infected Vero cells. Our evidence showed that the treatment with 0.3 mM ZnSO strongly inhibited the replication of virus progeny (MOI 0.001) at least 68-fold less. On the other hand, the IC50 demonstrated that the highest activity of ZnSO was at the 0.23 mM concentration.
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http://dx.doi.org/10.1007/s12011-019-01728-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7090960PMC
February 2020

The Role of microRNAs in the Viral Infections.

Curr Pharm Des 2018 ;24(39):4659-4667

Computational Optics Research Group, Advanced Institute of Materials Science, Ton Duc Thang University, Ho Chi Minh City, Vietnam.

MicroRNAs (miRNAs) are non-coding RNAs with 19 to 24 nucleotides which are evolutionally conserved. MicroRNAs play a regulatory role in many cellular functions such as immune mechanisms, apoptosis, and tumorigenesis. The main function of miRNAs is the post-transcriptional regulation of gene expression via mRNA degradation or inhibition of translation. In fact, many of them act as an oncogene or tumor suppressor. These molecular structures participate in many physiological and pathological processes of the cell. The virus can also produce them for developing its pathogenic processes. It was initially thought that viruses without nuclear replication cycle such as Poxviridae and RNA viruses can not code miRNA, but recently, it has been proven that RNA viruses can also produce miRNA. The aim of this articles is to describe viral miRNAs biogenesis and their effects on cellular and viral genes.
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http://dx.doi.org/10.2174/1381612825666190110161034DOI Listing
November 2019

Prevalence of Influenza A(H1N1)pdm09 Virus Resistant to Oseltamivir in Shiraz, Iran, During 2012 - 2013.

Jundishapur J Microbiol 2015 Aug 29;8(8):e23690. Epub 2015 Aug 29.

Department of Bacteriology and Virology, Shiraz University of Medical Sciences, Shiraz, IR Iran.

Background: Oseltamivir has been used as a drug of choice for the prophylaxis and treatment of human influenza A(H1N1)pdm09 infection across the world. However, the most frequently identified oseltamivir resistant virus, influenza A(H1N1)pdm09, exhibit the H275Y substitution in NA gene.

Objectives: This study aimed to determine the prevalence and phylogenetic relationships of oseltamivir resistance in influenza A(H1N1)pdm09 viruses isolated in Shiraz, Iran.

Patients And Methods: Throat swab samples were collected from 200 patients with influenza-like disease from December 2012 until February 2013. A total of 77 influenza A(H1N1)pdm09 positive strains were identified by real-time polymerase chain reaction (PCR). Oseltamivir resistance was detected using quantal assay and nested-PCR method. The NA gene sequencing was conducted to detect oseltamivir-resistant mutants and establish the phylogeny of the prevalent influenza variants.

Results: Our results revealed that A(H1N1)pdm09 viruses present in these samples were susceptible to oseltamivir, and contained 5 site specific mutations (V13G, V106I, V241I, N248D, and N369K) in NA gene. These mutations correlated with increasing expression and enzymatic activity of NA protein in the influenza A(H1N1)pdm09 viruses, which were closely related to a main influenza A(H1N1)pdm09 cluster isolated around the world.

Conclusions: A(H1N1)pdm09 viruses, identified in this study in Shiraz, Iran, contained 5 site specific mutations and were susceptible to oseltamivir.
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http://dx.doi.org/10.5812/jjm.23690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4600350PMC
August 2015

Antigenic Variation of the Haemagglutinin Gene of the Influenza A (H1N1) pdm09 Virus Circulating in Shiraz, February-April 2013.

Iran J Immunol 2015 Sep;12(3):198-208

Department of Bacteriology and Virology, Shiraz University of Medical Sciences, Shiraz, Iran, e-mail:

Background: A new pandemic influenza A (H1N1) emerged in April 2009, causing considerable morbidity and mortality. Since mutations in the haemagglutinin (HA) may influence the antigenicity and pathogenicity of the virus, continued epidemiological and molecular characterization for the effective control of pandemic flu and developing of more appropriate vaccine is crucial.

Objective: To monitor the molecular evolution of A (H1N1) pdm09 viruses in a specific time period in Shiraz, Southern Iran.

Methods: A total of 200 samples were collected from February-April 2013. HA gene of the isolates was amplified and sequenced. Phylogenetic analysis of the HA gene was performed.

Results: Out of 200 samples, a total of 77 (38.5%) samples were confirmed as A (H1N1) pdm09 virus using Real-time PCR method. Nucleotide similarity of our study strains with respect to reference strain A/California/07/2009 (H1N1) was 97.5%-98.5%. Phylogenetic analysis of our study strains indicated that the dominant A (H1N1) pdm09 clade was clade 7 and the dominant genetic group in circulating strains in Shiraz was genetic group 6. Some of our study strains showed substitutions at or in the vicinity of the antigenic sites of the HA1 region which may affect the efficacy of the vaccine.

Conclusion: Our study strains showed a high homology to the vaccine strain. Our findings confirm the genetic variability of influenza A (H1N1) pdm09 and highlight the necessity of continuous molecular study of the virus for effective management of influenza.
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http://dx.doi.org/IJIv12i3A5DOI Listing
September 2015

In Silico Functional and Structural Characterization of H1N1 Influenza A Viruses Hemagglutinin, 2010-2013, Shiraz, Iran.

Acta Biotheor 2015 Jun 12;63(2):183-202. Epub 2015 May 12.

Influenza Research Center, Department of Bacteriology and Virology, Shiraz University of Medical Sciences, 71348-45794, Shiraz, Iran,

Hemagglutinin (HA) is a major virulence factor of influenza viruses and plays an important role in viral pathogenesis. Analysis of amino acid changes, epitopes' regions, glycosylation and phosphorylation sites have greatly contributed to the development of new generations of vaccine. The hemagglutinins of 10 selected isolates, 8 of 2010 and 2 of 2013 samples were sequenced and analyzed by several bioinformatic softwares and the results were compared with those of 3 vaccine isolates. The study detected several amino acid changes related to altered epitopes' sites, modification sites and physico-chemical properties. The results showed some conserved modification sites in HA structure. This study is the first analytical research on isolates obtained from Shiraz, Iran, and our results can be used to better understand the genetic diversity and antigenic variations in Iranian and Asian H1N1 pathogenic strains.
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http://dx.doi.org/10.1007/s10441-015-9260-1DOI Listing
June 2015