Global Origin and Transmission of Hepatitis C Virus Nonstructural Protein 3 Q80K Polymorphism

2014 | J Infect Dis

Program(s): Laboratory |

Abstract:

Hepatitis C virus (HCV) has a naturally occurring polymorphism, Q80K, in the nonstructural protein 3 (NS3) gene encoding the viral protease, which has been associated with reduced susceptibility to the direct-acting antiviral inhibitor simeprevir. Q80K is observed predominantly in HCV genotype 1a and seldom in other HCV genotypes; moreover, it has a markedly high prevalence in the United States. Here, we reconstruct the evolutionary history of this polymorphism to investigate why it is so highly localized in prevalence and whether it is stably transmitted between hosts. We found that the majority (96%) of HCV infections carrying Q80K were descended from a single lineage in which a Q80K substitution occurred around the 1940s in the United States, which implies that this polymorphism is likely highly transmissible. Furthermore, we identified 2 other substitutions in NS3 that may interact with Q80K and contribute to its stability. Our results imply that the current distribution and prevalence of Q80K are unlikely to change significantly in the short term.

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McCloskey R

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Tel: 604-806-8477 | Fax: 604-806-9044
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© Copyright BC Centre for Excellence in HIV/AIDS
St. Paul's Hospital 608–1081 Burrard Street, Vancouver, BC, Canada V6Z 1Y6
Tel: 604-806-8477 | Fax: 604-806-9044
General inquiries: info@bccfe.ca
Media inquiries: communications@bccfe.ca
(Please do not use any of these email addresses to send personal information or book an appointment. To book appointments or contact the H2H clinic, please call 604-416-1517 or fax: 604-564-4893. Do not send your or your client's personal information via email.)

Our work serves clients and communities across British Columbia on lands and waters cared for and nurtured by the many distinct First Nations across the province. The BC-CfE humbly and gratefully acknowledge the stewards of these lands, particularly the xʷməθkʷəy̓əm (Musqueam), Sḵwx̱wú7mesh (Squamish), and səl̓ílwətaʔ (Tsleil-Waututh) on whose unceded, traditional and ancestral territories our offices are located.