PMID- 11460164
OWN - NLM
STAT- MEDLINE
DCOM- 20010816
LR  - 20081121
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 412
IP  - 6844
DP  - 2001 Jul 19
TI  - Evolution and transmission of stable CTL escape mutations in HIV infection.
PG  - 334-8
AB  - Increasing evidence indicates that potent anti-HIV-1 activity is mediated by 
      cytotoxic T lymphocytes (CTLs); however, the effects of this immune pressure on 
      viral transmission and evolution have not been determined. Here we investigate 
      mother-child transmission in the setting of human leukocyte antigen (HLA)-B27 
      expression, selected for analysis because it is associated with prolonged immune 
      containment in adult infection. In adults, mutations in a dominant and highly 
      conserved B27-restricted Gag CTL epitope lead to loss of recognition and disease 
      progression. In mothers expressing HLA-B27 who transmit HIV-1 perinatally, we 
      document transmission of viruses encoding CTL escape variants in this dominant 
      Gag epitope that no longer bind to B27. Their infected infants target an 
      otherwise subdominant B27-restricted epitope and fail to contain HIV replication. 
      These CTL escape variants remain stable without reversion in the absence of the 
      evolutionary pressure that originally selected the mutation. These data suggest 
      that CTL escape mutations in epitopes associated with suppression of viraemia 
      will accumulate as the epidemic progresses, and therefore have important 
      implications for vaccine design.
FAU - Goulder, P J
AU  - Goulder PJ
AD  - Partners AIDS Research Center, Massachusetts General Hospital and Division of 
      AIDS, Harvard Medical School, Boston, Massachusetts 02114, USA. 
      goulder@helix.mg.harvard.edu
FAU - Brander, C
AU  - Brander C
FAU - Tang, Y
AU  - Tang Y
FAU - Tremblay, C
AU  - Tremblay C
FAU - Colbert, R A
AU  - Colbert RA
FAU - Addo, M M
AU  - Addo MM
FAU - Rosenberg, E S
AU  - Rosenberg ES
FAU - Nguyen, T
AU  - Nguyen T
FAU - Allen, R
AU  - Allen R
FAU - Trocha, A
AU  - Trocha A
FAU - Altfeld, M
AU  - Altfeld M
FAU - He, S
AU  - He S
FAU - Bunce, M
AU  - Bunce M
FAU - Funkhouser, R
AU  - Funkhouser R
FAU - Pelton, S I
AU  - Pelton SI
FAU - Burchett, S K
AU  - Burchett SK
FAU - McIntosh, K
AU  - McIntosh K
FAU - Korber, B T
AU  - Korber BT
FAU - Walker, B D
AU  - Walker BD
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (DNA, Viral)
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (HLA-B27 Antigen)
SB  - IM
MH  - Adult
MH  - Child
MH  - DNA, Viral
MH  - Disease Progression
MH  - Epitopes, T-Lymphocyte/genetics
MH  - Female
MH  - HIV Infections/genetics/immunology/*transmission/virology
MH  - HIV-1/*genetics/immunology
MH  - HLA-B27 Antigen/immunology
MH  - Histocompatibility Testing
MH  - Humans
MH  - Infectious Disease Transmission, Vertical
MH  - *Mutation
MH  - T-Lymphocytes, Cytotoxic/*immunology
EDAT- 2001/07/19 10:00
MHDA- 2001/08/17 10:01
CRDT- 2001/07/19 10:00
PHST- 2001/07/19 10:00 [pubmed]
PHST- 2001/08/17 10:01 [medline]
PHST- 2001/07/19 10:00 [entrez]
AID - 35085576 [pii]
AID - 10.1038/35085576 [doi]
PST - ppublish
SO  - Nature. 2001 Jul 19;412(6844):334-8. doi: 10.1038/35085576.