adaptation to human populations is revealed by within-host polymorphisms in hiv-1 and hepatitis c virus适应人群是揭示了宿主中的多态性在hiv - 1和丙型肝炎病毒.pdfVIP

Adaptation to Human Populations Is Revealed by Within-Host Polymorphisms in HIV-1 and Hepatitis C Virus 1* 1 2 1,3,4 5 Art F. Y. Poon , Sergei L. Kosakovsky Pond , Phil Bennett , Douglas D. Richman , Andrew J. Leigh Brown , 1 Simon D. W. Frost 1 Department of Pathology, University of California San Diego, La Jolla, California, United States of America, 2 Science Park, University of Warwick, Coventry, United Kingdom, 3 School of Medicine, University of California San Diego, La Jolla, California, United States of America, 4 Veterans Affairs San Diego Healthcare System, San Diego, California, United States of America, 5 Institute of Evolutionary Biology, University of Edinburgh, Edinburgh, Scotland, United Kingdom CD8þ cytotoxic T-lymphocytes (CTLs) perform a critical role in the immune control of viral infections, including those caused by human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV). As a result, genetic variation at CTL epitopes is strongly influenced by host-specific selection for either escape from the immune response, or reversion due to the replicative costs of escape mutations in the absence of CTL recognition. Under strong CTL-mediated selection, codon positions within epitopes may immediately ‘‘toggle’’ in response to each host, such that genetic variation in the circulating virus population is shaped by rapid adaptation to immune variation in the host population. However, this hypothesis neglects the substantial genetic variation that accumulates in virus populations within hosts. Here, we evaluate this quantity for a large number of HIV-1– (n 3,000) and HCV-infected patients (n 2,600) by screening bulk RT-PCR sequences for sequencing ‘‘mixtures’’ (i.e., ambiguous nucleotides), which act as site