PMID- 36695358
OWN - NLM
STAT- MEDLINE
DCOM- 20230126
LR  - 20230921
IS  - 1473-5571 (Electronic)
IS  - 0269-9370 (Print)
IS  - 0269-9370 (Linking)
VI  - 37
IP  - 3
DP  - 2023 Mar 1
TI  - Host variation in type I interferon signaling genes (MX1), C-C chemokine receptor 
      type 5 gene, and major histocompatibility complex class I alleles in treated HIV+ 
      noncontrollers predict viral reservoir size.
PG  - 477-488
LID - 10.1097/QAD.0000000000003428 [doi]
AB  - OBJECTIVE: Prior genomewide association studies have identified variation in 
      major histocompatibility complex (MHC) class I alleles and C-C chemokine receptor 
      type 5 gene (CCR5Delta32) as genetic predictors of viral control, especially in 
      'elite' controllers, individuals who remain virally suppressed in the absence of 
      therapy. DESIGN: Cross-sectional genomewide association study. METHODS: We 
      analyzed custom whole exome sequencing and direct human leukocyte antigen (HLA) 
      typing from 202 antiretroviral therapy (ART)-suppressed HIV+ noncontrollers in 
      relation to four measures of the peripheral CD4+ T-cell reservoir: HIV intact 
      DNA, total (t)DNA, unspliced (us)RNA, and RNA/DNA. Linear mixed models were 
      adjusted for potential covariates including age, sex, nadir CD4+ T-cell count, 
      pre-ART HIV RNA, timing of ART initiation, and duration of ART suppression. 
      RESULTS: Previously reported 'protective' host genetic mutations related to viral 
      setpoint (e.g. among elite controllers) were found to predict smaller HIV 
      reservoir size. The HLA 'protective' B *57:01 was associated with significantly 
      lower HIV usRNA (q = 3.3 x 10-3), and among the largest subgroup, European 
      ancestry individuals, the CCR5Delta32 deletion was associated with smaller HIV tDNA 
      (P = 4.3 x 10-3) and usRNA (P = 8.7 x 10-3). In addition, genomewide analysis 
      identified several single nucleotide polymorphisms in MX1 (an interferon 
      stimulated gene) that were significantly associated with HIV tDNA (q = 0.02), and 
      the direction of these associations paralleled MX1 gene eQTL expression. 
      CONCLUSIONS: We observed a significant association between previously reported 
      'protective' MHC class I alleles and CCR5Delta32 with the HIV reservoir size in 
      noncontrollers. We also found a novel association between MX1 and HIV total DNA 
      (in addition to other interferon signaling relevant genes, PPP1CB, DDX3X). These 
      findings warrant further investigation in future validation studies.
CI  - Copyright (c) 2022 The Author(s). Published by Wolters Kluwer Health, Inc.
FAU - Siegel, David A
AU  - Siegel DA
AD  - Department of Medicine, Division of HIV, Infectious Diseases & Global Medicine.
FAU - Thanh, Cassandra
AU  - Thanh C
AD  - Department of Medicine, Division of Experimental Medicine.
FAU - Wan, Eunice
AU  - Wan E
AD  - Institute of Human Genetics.
FAU - Hoh, Rebecca
AU  - Hoh R
AD  - Department of Medicine, Division of HIV, Infectious Diseases & Global Medicine.
FAU - Hobbs, Kristen
AU  - Hobbs K
AD  - Department of Medicine, Division of Experimental Medicine.
FAU - Pan, Tony
AU  - Pan T
AD  - Department of Medicine, Division of Experimental Medicine.
FAU - Gibson, Erica A
AU  - Gibson EA
AD  - Department of Medicine, Division of Experimental Medicine.
FAU - Kroetz, Deanna L
AU  - Kroetz DL
AD  - Department of Bioengineering and Therapeutic Sciences.
FAU - Martin, Jeffrey
AU  - Martin J
AD  - Department of Biostatistics & Epidemiology, University of California San 
      Francisco, California.
FAU - Hecht, Frederick
AU  - Hecht F
AD  - Department of Medicine, Division of HIV, Infectious Diseases & Global Medicine.
FAU - Pilcher, Christopher
AU  - Pilcher C
AD  - Department of Medicine, Division of HIV, Infectious Diseases & Global Medicine.
FAU - Martin, Maureen
AU  - Martin M
AD  - Basic Science Program, Frederick National Laboratory for Cancer Research, 
      National Cancer Institute, Frederick, and Laboratory of Integrative Cancer 
      Immunology, Center for Cancer Research, National Cancer Institute, Bethesda, 
      Maryland.
FAU - Carrington, Mary
AU  - Carrington M
AD  - Basic Science Program, Frederick National Laboratory for Cancer Research, 
      National Cancer Institute, Frederick, and Laboratory of Integrative Cancer 
      Immunology, Center for Cancer Research, National Cancer Institute, Bethesda, 
      Maryland.
AD  - Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts.
FAU - Pillai, Satish
AU  - Pillai S
AD  - Vitalant Blood Bank, San Francisco, California.
FAU - Busch, Michael P
AU  - Busch MP
AD  - Vitalant Blood Bank, San Francisco, California.
FAU - Stone, Mars
AU  - Stone M
AD  - Vitalant Blood Bank, San Francisco, California.
FAU - Levy, Claire N
AU  - Levy CN
AD  - Department of Obstetrics and Gynecology.
FAU - Huang, Meei-Li
AU  - Huang ML
AD  - Department of Laboratory Medicine and Pathology, University of Washington.
AD  - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 
      Seattle, Washington, USA.
FAU - Roychoudhury, Pavitra
AU  - Roychoudhury P
AD  - Department of Laboratory Medicine and Pathology, University of Washington.
AD  - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 
      Seattle, Washington, USA.
FAU - Hladik, Florian
AU  - Hladik F
AD  - Department of Obstetrics and Gynecology.
AD  - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 
      Seattle, Washington, USA.
FAU - Jerome, Keith R
AU  - Jerome KR
AD  - Department of Laboratory Medicine and Pathology, University of Washington.
AD  - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 
      Seattle, Washington, USA.
FAU - Kiem, Hans-Peter
AU  - Kiem HP
AD  - Department of Laboratory Medicine and Pathology, University of Washington.
AD  - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 
      Seattle, Washington, USA.
FAU - Henrich, Timothy J
AU  - Henrich TJ
AD  - Department of Bioengineering and Therapeutic Sciences.
FAU - Deeks, Steven G
AU  - Deeks SG
AD  - Department of Medicine, Division of HIV, Infectious Diseases & Global Medicine.
FAU - Lee, Sulggi A
AU  - Lee SA
AD  - Department of Medicine, Division of HIV, Infectious Diseases & Global Medicine.
LA  - eng
GR  - R01 AI143464/AI/NIAID NIH HHS/United States
GR  - U19 AI096109/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20221118
PL  - England
TA  - AIDS
JT  - AIDS (London, England)
JID - 8710219
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (HLA Antigens)
RN  - 63231-63-0 (RNA)
RN  - 0 (Receptors, Chemokine)
RN  - 0 (Interferon Type I)
RN  - 0 (MX1 protein, human)
RN  - 0 (Myxovirus Resistance Proteins)
SB  - IM
MH  - Humans
MH  - *HIV Infections/drug therapy/genetics
MH  - Alleles
MH  - CD8-Positive T-Lymphocytes
MH  - Cross-Sectional Studies
MH  - *HIV-1/genetics
MH  - Histocompatibility Antigens Class I/genetics
MH  - HLA Antigens
MH  - RNA
MH  - Major Histocompatibility Complex
MH  - Receptors, Chemokine/genetics
MH  - *Interferon Type I/metabolism
MH  - Viral Load
MH  - Myxovirus Resistance Proteins
PMC - PMC9894159
COIS- There are no conflicts of interest.
EDAT- 2023/01/26 06:00
MHDA- 2023/01/27 06:00
PMCR- 2023/02/02
CRDT- 2023/01/25 06:33
PHST- 2023/01/25 06:33 [entrez]
PHST- 2023/01/26 06:00 [pubmed]
PHST- 2023/01/27 06:00 [medline]
PHST- 2023/02/02 00:00 [pmc-release]
AID - 00002030-202303010-00011 [pii]
AID - AIDS-D-22-00405 [pii]
AID - 10.1097/QAD.0000000000003428 [doi]
PST - ppublish
SO  - AIDS. 2023 Mar 1;37(3):477-488. doi: 10.1097/QAD.0000000000003428. Epub 2022 Nov 
      18.