High Multiplicity Infection by HIV-1 in Men Who Have Sex with Men.
Elucidating virus-host interactions responsible for HIV-1 transmission is important for advancing HIV-1 prevention strategies. To this end, single genome amplification (SGA) and sequencing of HIV-1 within the context of a model of random virus evolution has made possible for the first time an unambiguous identification of transmitted/founder viruses and a precise estimation of their numbers. Here, we applied this approach to HIV-1 env analyses in a cohort of acutely infected men who have sex with men (MSM) and found that a high proportion (10 of 28; 36%) had been productively infected by more than one virus. In subjects with multivariant transmission, the minimum number of transmitted viruses ranged from 2 to 10 with viral recombination leading to rapid and extensive genetic shuffling among virus lineages. A combined analysis of these results, together with recently published findings based on identical SGA methods in largely heterosexual (HSX) cohorts, revealed a significantly higher frequency of multivariant transmission in MSM than in HSX [19 of 50 subjects (38%) versus 34 of 175 subjects (19%); Fisher's exact p = 0.008]. To further evaluate the SGA strategy for identifying transmitted/founder viruses, we analyzed 239 overlapping 5' and 3' half genome or env-only sequences from plasma viral RNA (vRNA) and blood mononuclear cell DNA in an MSM subject who had a particularly well-documented virus exposure history 3-6 days before symptom onset and 14-17 days before peak plasma viremia (47,600,000 vRNA molecules/ml). All 239 sequences coalesced to a single transmitted/founder virus genome in a time frame consistent with the clinical history, and a molecular clone of this genome encoded replication competent virus in accord with model predictions. Higher multiplicity of HIV-1 infection in MSM compared with HSX is consistent with the demonstrably higher epidemiological risk of virus acquisition in MSM and could indicate a greater challenge for HIV-1 vaccines than previously recognized.
Li
Hui
H
Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
Bar
Katharine J
KJ
Wang
Shuyi
S
Decker
Julie M
JM
Chen
Yalu
Y
Sun
Chuanxi
C
Salazar-Gonzalez
Jesus F
JF
Salazar
Maria G
MG
Learn
Gerald H
GH
Morgan
Charity J
CJ
Schumacher
Joseph E
JE
Hraber
Peter
P
Giorgi
Elena E
EE
Bhattacharya
Tanmoy
T
Korber
Bette T
BT
Perelson
Alan S
AS
Eron
Joseph J
JJ
Cohen
Myron S
MS
Hicks
Charles B
CB
Haynes
Barton F
BF
Markowitz
Martin
M
Keele
Brandon F
BF
Hahn
Beatrice H
BH
Shaw
George M
GM
D004196:Disease Outbreaks / Q000706:statistics & numerical data; D019143:Evolution, Molecular; D014644:Genetic Variation; D016679:Genome, Viral; D015658:HIV Infections / Q000453:epidemiology / Q000517:prevention & control / Q000635:transmission; D015497:HIV-1 / Q000235:genetics* / Q000254:growth & development* / Q000472:pathogenicity; D020010:Heterosexuality / Q000706:statistics & numerical data; D018451:Homosexuality, Male / Q000706:statistics & numerical data*; D006801:Humans; D008297:Male; D008957:Models, Genetic; D011995:Recombination, Genetic / Q000235:genetics; D012307:Risk Factors; D012725:Sexual Behavior / Q000706:statistics & numerical data*; D014774:Virulence; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics
D054299:env Gene Products, Human Immunodeficiency Virus