Genetic diversity of NS5A protein from hepatitis C virus genotype 3a and its relationship to therapy response
- PMID: 20178583
- PMCID: PMC2838888
- DOI: 10.1186/1471-2334-10-36
Genetic diversity of NS5A protein from hepatitis C virus genotype 3a and its relationship to therapy response
Abstract
Background: The quasispecies nature of HCV may have important implications for viral persistence, pathogenicity and resistance to antiviral agents. The variability of one of the viral proteins, NS5A, is believed to be related to the response to IFN therapy, the standard treatment for infection. In this study we analyzed the quasispecies composition of NS5A protein in patients infected with HCV genotype 3a, before IFN therapy.
Methods: Viral RNA was isolated from samples of 12 patients: four sustained virological responders (SVR), four non-responders (NR), and four end-of-treatment responders (ETR). cDNA was synthesized, the NS5A region was amplified and the fragments obtained were cloned. Fifteen clones from each patient were sequenced with eight primers, generating 179 contigs.
Results: Higher values for substitution (either synonymous or non-synonymous) and for distance were found in the SVR group. However, the NR group showed relatively more non-synonymous mutations than the other groups, owing to the higher values of dN/dS in complete NS5A and most specific regions. Overall, NS5A protein is undergoing purifying selection, since all dN/dS ratios values are below 0.5.
Conclusions: Our study provides an overview of the genetic variability of complete NS5A protein in HCV genotype 3a.
Figures



Similar articles
-
Analysis of HCV quasispecies dynamic under selective pressure of combined therapy.BMC Infect Dis. 2013 Feb 1;13:61. doi: 10.1186/1471-2334-13-61. BMC Infect Dis. 2013. PMID: 23374983 Free PMC article.
-
Quasispecies of hepatitis C virus genotype 1 and treatment outcome with peginterferon and ribavirin.Infect Genet Evol. 2009 Jul;9(4):689-98. doi: 10.1016/j.meegid.2008.11.001. Epub 2008 Nov 21. Infect Genet Evol. 2009. PMID: 19063998
-
Response to combination therapy of HCV 3a infected Pakistani patients and the role of NS5A protein.Virol J. 2011 May 25;8:258. doi: 10.1186/1743-422X-8-258. Virol J. 2011. PMID: 21609495 Free PMC article.
-
Quasispecies evolution in NS5A region of hepatitis C virus genotype 1b during interferon or combined interferon-ribavirin therapy.World J Gastroenterol. 2007 Feb 28;13(8):1195-203. doi: 10.3748/wjg.v13.i8.1195. World J Gastroenterol. 2007. PMID: 17451199 Free PMC article.
-
Sequencing of E2 and NS5A regions of HCV genotype 3a in Brazilian patients with chronic hepatitis.Mem Inst Oswaldo Cruz. 2010 Feb;105(1):92-8. doi: 10.1590/s0074-02762010000100014. Mem Inst Oswaldo Cruz. 2010. PMID: 20209336
Cited by
-
Copy number variation of genes involved in the hepatitis C virus-human interactome.Sci Rep. 2016 Aug 11;6:31340. doi: 10.1038/srep31340. Sci Rep. 2016. PMID: 27510840 Free PMC article.
-
Study of PKRBD in HCV genotype 3a infected patients in response to interferon therapy in Pakistani population.Virol J. 2013 Dec 9;10:352. doi: 10.1186/1743-422X-10-352. Virol J. 2013. PMID: 24321105 Free PMC article.
-
Analysis of the Enzymatic Activity of an NS3 Helicase Genotype 3a Variant Sequence Obtained from a Relapse Patient.PLoS One. 2015 Dec 10;10(12):e0144638. doi: 10.1371/journal.pone.0144638. eCollection 2015. PLoS One. 2015. PMID: 26658750 Free PMC article.
-
Insights From Deep Sequencing of the HBV Genome-Unique, Tiny, and Misunderstood.Gastroenterology. 2019 Jan;156(2):384-399. doi: 10.1053/j.gastro.2018.07.058. Epub 2018 Sep 27. Gastroenterology. 2019. PMID: 30268787 Free PMC article. Review.
-
Analysis of HCV quasispecies dynamic under selective pressure of combined therapy.BMC Infect Dis. 2013 Feb 1;13:61. doi: 10.1186/1471-2334-13-61. BMC Infect Dis. 2013. PMID: 23374983 Free PMC article.
References
-
- Silva LK, Parana R, Souza SP, Berby F, Kay A, Trepo C, Santana N, Cotrim H, Lyra LG, Reis MG. Hepatitis C virus genotypes in a northeastern area of Brazil. Am J Trop Med Hyg. 2000;62(2):257–260. - PubMed
Publication types
MeSH terms
Substances
Associated data
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
- Actions
LinkOut - more resources
Full Text Sources