PMID- 33710015
OWN - NLM
STAT- MEDLINE
DCOM- 20210625
LR  - 20230921
IS  - 1473-5571 (Electronic)
IS  - 0269-9370 (Print)
IS  - 0269-9370 (Linking)
VI  - 35
IP  - 8
DP  - 2021 Jul 1
TI  - HLA-associated preadaptation in HIV Vif is associated with higher set point viral 
      load and faster CD4+ decline in Zambian transmission pairs.
PG  - 1157-1165
LID - 10.1097/QAD.0000000000002868 [doi]
AB  - OBJECTIVE S: We investigated the relationship between human leukocyte antigen 
      (HLA)-associated preadaptation for the entire subtype C HIV-1 proteome of the 
      transmitted founder virus and subsequent HIV-1 disease progression in a cohort of 
      heterosexual linked transmission pairs in Zambia. DESIGN: An adaptation model was 
      used to calculate an adaptation score for each virus-HLA combination in order to 
      quantify the degree of preadaptation of the transmitted virus to the linked 
      recipient's HLA alleles. These scores were then assessed for their relationship 
      to viral load and longitudinal CD4+ decline in the recipient. METHODS: Viral RNA 
      was extracted from the plasma of the donor partner and the linked recipient near 
      the time of transmission, as well as longitudinally from the linked recipient. 
      Viral adaptation scores were calculated for each individual and each protein in 
      the subtype C HIV-1 proteome. RESULTS: The majority of HLA-associated sites were 
      located in Gag, Pol and Nef; however, proportional to protein length, the 
      accessory and regulatory proteins contained a relatively high proportion of 
      HLA-associated sites. Over the course of infection, HLA-mediated immune 
      adaptation increased for all proteins except Vpu and gp120. Preadaptation was 
      positively associated with higher early set point viral load and faster CD4+ 
      decline. When examined by protein, preadaptation in Pol and Vif were 
      statistically significantly associated with these markers of disease progression. 
      CONCLUSION: Adaptation in Pol had the greatest impact on viral control. Despite 
      containing a large proportion of HLA-associated sites, Vif was the only 
      regulatory or accessory protein for which preadaptation significantly correlated 
      with disease progression.
CI  - Copyright (c) 2021 Wolters Kluwer Health, Inc. All rights reserved.
FAU - Connolly, Sarah
AU  - Connolly S
AD  - Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, 
      Atlanta, Georgia.
FAU - Carlson, Jonathan M
AU  - Carlson JM
AD  - Microsoft Research, Redmond, Washington, USA.
FAU - Schaefer, Malinda
AU  - Schaefer M
AD  - Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, 
      Atlanta, Georgia.
FAU - Bere, Alfred
AU  - Bere A
AD  - Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, 
      Atlanta, Georgia.
FAU - Kilembe, William
AU  - Kilembe W
AD  - Zambia-Emory HIV Research Project, Lusaka, Zambia.
FAU - Allen, Susan
AU  - Allen S
AD  - Zambia-Emory HIV Research Project, Lusaka, Zambia.
AD  - Department of Global Health, Rollins School of Public Health.
AD  - Department of Pathology and Laboratory Medicine, Emory University, Atlanta, 
      Georgia, USA.
FAU - Hunter, Eric
AU  - Hunter E
AD  - Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, 
      Atlanta, Georgia.
AD  - Zambia-Emory HIV Research Project, Lusaka, Zambia.
AD  - Department of Pathology and Laboratory Medicine, Emory University, Atlanta, 
      Georgia, USA.
LA  - eng
GR  - P30 AI050409/AI/NIAID NIH HHS/United States
GR  - P51 OD011132/OD/NIH HHS/United States
GR  - R01 AI051231/AI/NIAID NIH HHS/United States
GR  - R01 AI064060/AI/NIAID NIH HHS/United States
GR  - R01 MH095503/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - AIDS
JT  - AIDS (London, England)
JID - 8710219
RN  - 0 (HLA Antigens)
RN  - 0 (vif Gene Products, Human Immunodeficiency Virus)
RN  - 0 (vif protein, Human immunodeficiency virus 1)
RN  - 0 (vif protein, Human immunodeficiency virus 2)
SB  - IM
MH  - CD4-Positive T-Lymphocytes
MH  - *HIV Infections
MH  - HLA Antigens
MH  - Humans
MH  - Viral Load
MH  - Zambia
MH  - vif Gene Products, Human Immunodeficiency Virus
PMC - PMC8546905
MID - NIHMS1680223
COIS- Conflicts of Interest The authors have no conflicts of interest to declare.
EDAT- 2021/03/13 06:00
MHDA- 2021/06/29 06:00
PMCR- 2022/07/01
CRDT- 2021/03/12 12:31
PHST- 2021/03/13 06:00 [pubmed]
PHST- 2021/06/29 06:00 [medline]
PHST- 2021/03/12 12:31 [entrez]
PHST- 2022/07/01 00:00 [pmc-release]
AID - 00002030-202107010-00001 [pii]
AID - 10.1097/QAD.0000000000002868 [doi]
PST - ppublish
SO  - AIDS. 2021 Jul 1;35(8):1157-1165. doi: 10.1097/QAD.0000000000002868.