HIV evolution: CTL escape mutation and reversion after transmission

Leslie, Alasdair; Pfafferott, Katja; Chetty, Polan; Draenert, Rika; Addo, Marylyn M.; Feeney, Margaret E.; Tang, Yanhua; Holmes, Edward C.; Allen, Todd M.; Prado, Julia G.; Altfeld, Marcus; Berthou, Christian; Dixon, Catherine; Ramduth, Danni; Jeena, Prakash; Thomas, Stéphanie; John, Anne St.; Roach, Timothy; Kupfer, Bernd; Luzzi, Graz; Edwards, Anne; Taylor, Graham P.; Lyall, Hermione; Tudor‐Williams, Gareth; Novelli, Vas; Martínez-Picado, Javier; Kiepiela, Photini; Walker, Bruce D.; Goulder, Philip

doi:10.1038/nm992

Cited by 764 publications

(950 citation statements)

References 42 publications

Supporting

Mentioning

898

Contrasting

Unclassified

Order By: Relevance

“…Protective HLA alleles, such as HLA-B*57, -B*58, and -B*27, select Gag mutations affecting viral replication in Caucasians and Africans (36)(37)(38)(39)(40)(41) that may also provide some clinical benefit if they are transmitted to hosts lacking these alleles (42,43). HLA-B*57, -B*58, and -B*27 are not present at appreciable frequencies in Japan (23).…”

Section: Discussionmentioning

confidence: 99%

Host-Specific Adaptation of HIV-1 Subtype B in the Japanese Population

Chikata

Carlson

Tamura

et al. 2014

J Virol

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Host-Specific Adaptation of HIV-1 Subtype B in the Japanese Population

Chikata

Carlson

Tamura

et al. 2014

J Virol

View full text Add to dashboard Cite

“…Although subdominant epitopes elicit fewer responding T cells, they are ostensibly protective in particular cohorts of patients with active infection (5,6,9,21,76). The most direct evidence that subdominant responses are important for HIV-1 control comes from a recent report in macaques that spontaneously controlled pathogenic SIV.…”

Section: Discussionmentioning

confidence: 99%

Availability of a Diversely Avid CD8+ T Cell Repertoire Specific for the Subdominant HLA-A2-Restricted HIV-1 Gag p2419–27 Epitope

Schaubert

Price

Frahm

et al. 2007

The Journal of Immunology

View full text Add to dashboard Cite

HLA-A2-restricted CTL responses to immunodominant HIV-1 epitopes do not appear to be very effective in the control of viral replication in vivo. In this study, we studied human CD8+ T cell responses to the subdominant HLA-A2-restricted epitope TV9 (Gag p2419–27, TLNAWVKVV) to explore the possibility of increasing its immune recognition. We confirmed in a cohort of 313 patients, infected by clade B or clade C viruses, that TV9 is rarely recognized. Of interest, the functional sensitivity of the TV9 response can be relatively high. The potential T cell repertoires for TV9 and the characteristics of constituent clonotypes were assessed by ex vivo priming of circulating CD8+ T cells from healthy seronegative donors. TV9-specific CTLs capable of suppressing viral replication in vitro were readily generated, suggesting that the cognate T cell repertoire is not limiting. However, these cultures contained multiple discrete populations with a range of binding avidities for the TV9 tetramer and correspondingly distinct functional dependencies on the CD8 coreceptor. The lack of dominant clonotypes was not affected by the stage of maturation of the priming dendritic cells. Cultures primed by dendritic cells transduced to present endogenous TV9 were also incapable of clonal maturation. Thus, a diffuse TCR repertoire appeared to be an intrinsic characteristic of TV9-specific responses. These data indicate that subdominance is not a function of poor immunogenicity, cognate TCR repertoire availability, or the potential avidity properties thereof, but rather suggest that useful responses to this epitope are suppressed by competing CD8+ T cell populations during HIV-1 infection.

show abstract

“…MHC-defined Indian rhesus macaques provide an excellent resource for elucidating the influence of particular MHC alleles in SIV disease progression. Both the human allele HLA-B*57 and the rhesus allele Mamu-B*17 are overrepresented among long-term nonprogressors (21,31), and both alleles present immunologically relevant HIV-or SIV-derived peptides to CD8 ϩ T cells (15,16,22,23). However, not all HLA-B*57-positive infected individuals or Mamu-B*17-positive infected rhesuses suppress viral replication (21,31).…”

mentioning

confidence: 99%

Control of Simian Immunodeficiency Virus SIVmac239 Is Not Predicted by Inheritance of Mamu-B * 17 -Containing Haplotypes

Wojcechowskyj

Yant

Wiseman

et al. 2007

J Virol

View full text Add to dashboard Cite

It is well established that host genetics, especially major histocompatibility complex (MHC) genes, are important determinants of human immunodeficiency virus disease progression. Studies with simian immunodeficiency virus (SIV)-infected Indian rhesus macaques have associated Mamu-B*17 with control of virus replication. Using microsatellite haplotyping of the 5-Mb MHC region, we compared disease progression among SIVmac239-infected Indian rhesus macaques that possess Mamu-B*17-containing MHC haplotypes that are identical by descent. We discovered that SIV-infected animals possessing identical Mamu-B*17-containing haplotypes had widely divergent disease courses. Our results demonstrate that the inheritance of a particular Mamu-B*17-containing haplotype is not sufficient to predict SIV disease outcome.

show abstract

HIV evolution: CTL escape mutation and reversion after transmission

Cited by 764 publications

References 42 publications

Host-Specific Adaptation of HIV-1 Subtype B in the Japanese Population

Host-Specific Adaptation of HIV-1 Subtype B in the Japanese Population

Availability of a Diversely Avid CD8+ T Cell Repertoire Specific for the Subdominant HLA-A2-Restricted HIV-1 Gag p2419–27 Epitope

Control of Simian Immunodeficiency Virus SIVmac239 Is Not Predicted by Inheritance of Mamu-B * 17 -Containing Haplotypes

Contact Info

Product

Resources

About