Global origin and transmission of hepatitis C virus nonstructural protein 3 Q80K polymorphism.
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.
BC Centre for Excellence in HIV/AIDS.
Rosemary M
RM
McCloskey
BC Centre for Excellence in HIV/AIDS.
Richard H
RH
Liang
BC Centre for Excellence in HIV/AIDS.
Jeffrey B
JB
Joy
BC Centre for Disease Control.
Mel
M
Krajden
BC Centre for Excellence in HIV/AIDS Department of Medicine, University of British Columbia, Vancouver, Canada.
Julio S G
JS
Montaner
BC Centre for Excellence in HIV/AIDS Department of Medicine, University of British Columbia, Vancouver, Canada.
P Richard
PR
Harrigan
BC Centre for Excellence in HIV/AIDS Department of Medicine, University of British Columbia, Vancouver, Canada.
Art F Y
AF
Poon
D000998:Antiviral Agents / Q000627:therapeutic use; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics*; D006526:Hepatitis C / Q000188:drug therapy / Q000821:virology*; D006575:Heterocyclic Compounds, 3-Ring / Q000627:therapeutic use; D006801:Humans; D011110:Polymorphism, Genetic / Q000235:genetics*; D015995:Prevalence; D011480:Protease Inhibitors / Q000627:therapeutic use; D000069616:Simeprevir; D013449:Sulfonamides / Q000627:therapeutic use; D017361:Viral Nonstructural Proteins / Q000235:genetics*
D000998:Antiviral Agents; D006575:Heterocyclic Compounds, 3-Ring; D011480:Protease Inhibitors; D013449:Sulfonamides; D017361:Viral Nonstructural Proteins; D000069616:Simeprevir
Q80K; ancestral reconstruction; hepatitis C virus; molecular phylogenetics; phylogeography; simeprevir; virus evolution