PMID- 18426987
OWN - NLM
STAT- MEDLINE
DCOM- 20080804
LR  - 20220129
IS  - 1540-9538 (Electronic)
IS  - 0022-1007 (Print)
IS  - 0022-1007 (Linking)
VI  - 205
IP  - 5
DP  - 2008 May 12
TI  - Transmission of HIV-1 Gag immune escape mutations is associated with reduced 
      viral load in linked recipients.
PG  - 1009-17
LID - 10.1084/jem.20072457 [doi]
AB  - In a study of 114 epidemiologically linked Zambian transmission pairs, we 
      evaluated the impact of human leukocyte antigen class I (HLA-I)-associated amino 
      acid polymorphisms, presumed to reflect cytotoxic T lymphocyte (CTL) escape in 
      Gag and Nef of the virus transmitted from the chronically infected donor, on the 
      plasma viral load (VL) in matched recipients 6 mo after infection. CTL escape 
      mutations in Gag and Nef were seen in the donors, which were subsequently 
      transmitted to recipients, largely unchanged soon after infection. We observed a 
      significant correlation between the number of Gag escape mutations targeted by 
      specific HLA-B allele-restricted CTLs and reduced VLs in the recipients. This 
      negative correlation was most evident in newly infected individuals, whose HLA 
      alleles were unable to effectively target Gag and select for CTL escape mutations 
      in this gene. Nef mutations in the donor had no impact on VL in the recipient. 
      Thus, broad Gag-specific CTL responses capable of driving virus escape in the 
      donor may be of clinical benefit to both the donor and recipient. In addition to 
      their direct implications for HIV-1 vaccine design, these data suggest that 
      CTL-induced viral polymorphisms and their associated in vivo viral fitness costs 
      could have a significant impact on HIV-1 pathogenesis.
FAU - Goepfert, Paul A
AU  - Goepfert PA
AD  - Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 
      35294, USA. paulg@uab.edu
FAU - Lumm, Wendy
AU  - Lumm W
FAU - Farmer, Paul
AU  - Farmer P
FAU - Matthews, Philippa
AU  - Matthews P
FAU - Prendergast, Andrew
AU  - Prendergast A
FAU - Carlson, Jonathan M
AU  - Carlson JM
FAU - Derdeyn, Cynthia A
AU  - Derdeyn CA
FAU - Tang, Jianming
AU  - Tang J
FAU - Kaslow, Richard A
AU  - Kaslow RA
FAU - Bansal, Anju
AU  - Bansal A
FAU - Yusim, Karina
AU  - Yusim K
FAU - Heckerman, David
AU  - Heckerman D
FAU - Mulenga, Joseph
AU  - Mulenga J
FAU - Allen, Susan
AU  - Allen S
FAU - Goulder, Philip J R
AU  - Goulder PJ
FAU - Hunter, Eric
AU  - Hunter E
LA  - eng
GR  - P30 AI050409/AI/NIAID NIH HHS/United States
GR  - G0501777/MRC_/Medical Research Council/United Kingdom
GR  - G0500384/MRC_/Medical Research Council/United Kingdom
GR  - AI-46995/AI/NIAID NIH HHS/United States
GR  - R01 AI041951/AI/NIAID NIH HHS/United States
GR  - R01 AI064060/AI/NIAID NIH HHS/United States
GR  - WT_/Wellcome Trust/United Kingdom
GR  - R01 AI046995/AI/NIAID NIH HHS/United States
GR  - AI-64060/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20080421
PL  - United States
TA  - J Exp Med
JT  - The Journal of experimental medicine
JID - 2985109R
RN  - 0 (Gene Products, gag)
RN  - 0 (HLA-B Antigens)
RN  - 0 (Histocompatibility Antigens Class I)
SB  - IM
MH  - Amino Acid Sequence
MH  - Base Sequence
MH  - Gene Products, gag/chemistry/*genetics/immunology
MH  - HIV-1/*genetics/immunology
MH  - HLA-B Antigens/genetics/immunology
MH  - Histocompatibility Antigens Class I/immunology
MH  - Humans
MH  - *Mutation
MH  - Polymorphism, Genetic
MH  - South Africa/epidemiology
MH  - *Viral Load
MH  - Zambia/epidemiology
PMC - PMC2373834
EDAT- 2008/04/23 09:00
MHDA- 2008/08/05 09:00
PMCR- 2008/11/12
CRDT- 2008/04/23 09:00
PHST- 2008/04/23 09:00 [pubmed]
PHST- 2008/08/05 09:00 [medline]
PHST- 2008/04/23 09:00 [entrez]
PHST- 2008/11/12 00:00 [pmc-release]
AID - jem.20072457 [pii]
AID - 20072457 [pii]
AID - 10.1084/jem.20072457 [doi]
PST - ppublish
SO  - J Exp Med. 2008 May 12;205(5):1009-17. doi: 10.1084/jem.20072457. Epub 2008 Apr 
      21.