TY - JOUR
T1 - Population-level immune-mediated adaptation in HIV-1 polymerase during the North American epidemic
AU - Kinloch, Natalie N.
AU - MacMillan, Daniel R.
AU - Le, Anh Q.
AU - Cotton, Laura A.
AU - Bangsberg, David R.
AU - Buchbinder, Susan
AU - Carrington, Mary
AU - Fuchs, Jonathan
AU - Richard Harrigan, P.
AU - Koblin, Beryl
AU - Kushel, Margot
AU - Markowitz, Martin
AU - Mayer, Kenneth
AU - Milloy, M. J.
AU - Schechter, Martin T.
AU - Wagner, Theresa
AU - Walker, Bruce D.
AU - Carlson, Jonathan M.
AU - Poon, Art F.Y.
AU - Brumme, Zabrina L.
N1 - Publisher Copyright:
© 2016, American Society for Microbiology.
PY - 2016
Y1 - 2016
N2 - Human leukocyte antigen (HLA) class I-associated polymorphisms in HIV-1 that persist upon transmission to HLA-mismatched hosts may spread in the population as the epidemic progresses. Transmission of HIV-1 sequences containing such adaptations may undermine cellular immune responses to the incoming virus in future hosts. Building upon previous work, we investigated the extent of HLA-associated polymorphism accumulation in HIV-1 polymerase (Pol) through comparative analysis of linked HIV-1/HLA class I genotypes sampled during historic (1979 to 1989; n=338) and modern (2001 to 2011; n=278) eras from across North America (Vancouver, BC, Canada; Boston, MA; New York, NY; and San Francisco, CA). Phylogenies inferred from historic and modern HIV-1 Pol sequences were star-like in shape, with an inferred most recent common ancestor (epidemic founder virus) sequence nearly identical to the modern North American subtype B consensus sequence. Nevertheless, modern HIV-1 Pol sequences exhibited roughly 2-fold-higher patristic (tip-to-tip) genetic distances than historic sequences, with HLA pressures likely driving ongoing diversification. Moreover, the frequencies of published HLA-associated polymorphisms in individuals lacking the selecting HLA class I allele was on average=2.5-fold higher in the modern than in the historic era, supporting their spread in circulation, though some remained stable in frequency during this time. Notably, polymorphisms restricted by protective HLA alleles appear to be spreading to a greater relative extent than others, though these increases are generally of modest absolute magnitude. However, despite evidence of polymorphism spread, North American hosts generally remain at relatively low risk of acquiring an HIV-1 polymerase sequence substantially preadapted to their HLA profiles, even in the present era.
AB - Human leukocyte antigen (HLA) class I-associated polymorphisms in HIV-1 that persist upon transmission to HLA-mismatched hosts may spread in the population as the epidemic progresses. Transmission of HIV-1 sequences containing such adaptations may undermine cellular immune responses to the incoming virus in future hosts. Building upon previous work, we investigated the extent of HLA-associated polymorphism accumulation in HIV-1 polymerase (Pol) through comparative analysis of linked HIV-1/HLA class I genotypes sampled during historic (1979 to 1989; n=338) and modern (2001 to 2011; n=278) eras from across North America (Vancouver, BC, Canada; Boston, MA; New York, NY; and San Francisco, CA). Phylogenies inferred from historic and modern HIV-1 Pol sequences were star-like in shape, with an inferred most recent common ancestor (epidemic founder virus) sequence nearly identical to the modern North American subtype B consensus sequence. Nevertheless, modern HIV-1 Pol sequences exhibited roughly 2-fold-higher patristic (tip-to-tip) genetic distances than historic sequences, with HLA pressures likely driving ongoing diversification. Moreover, the frequencies of published HLA-associated polymorphisms in individuals lacking the selecting HLA class I allele was on average=2.5-fold higher in the modern than in the historic era, supporting their spread in circulation, though some remained stable in frequency during this time. Notably, polymorphisms restricted by protective HLA alleles appear to be spreading to a greater relative extent than others, though these increases are generally of modest absolute magnitude. However, despite evidence of polymorphism spread, North American hosts generally remain at relatively low risk of acquiring an HIV-1 polymerase sequence substantially preadapted to their HLA profiles, even in the present era.
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U2 - 10.1128/JVI.02353-15
DO - 10.1128/JVI.02353-15
M3 - Article
C2 - 26559841
AN - SCOPUS:84958078538
SN - 0022-538X
VL - 90
SP - 1244
EP - 1258
JO - Journal of virology
JF - Journal of virology
IS - 3
ER -