HIV and SIV CTL escape: implications for vaccine design

@article{Goulder2004HIVAS,
  title={HIV and SIV CTL escape: implications for vaccine design},
  author={Philip J. R. Goulder and David I. Watkins},
  journal={Nature Reviews Immunology},
  year={2004},
  volume={4},
  pages={630-640}
}
Cytotoxic T lymphocytes (CTLs) have a central role in the successful control of immunodeficiency virus infection. Evasion of this immune response through CTL escape is therefore an important factor in HIV and simian immunodeficiency virus pathogenesis. During the course of an infection, the precise timing of the occurrence of escape mutations and their location in the viral genome can indicate the efficacy of certain CTL specificities and the cost to viral fitness of particular escape mutations… 
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References

SHOWING 1-10 OF 110 REFERENCES
Reversion of CTL escape–variant immunodeficiency viruses in vivo
TLDR
It is concluded that escape from CTL responses may exact a cost to viral fitness, and in the absence of selective pressure upon transmission to new hosts, these original escape mutations can be lost.
Late escape from an immunodominant cytotoxic T-lymphocyte response associated with progression to AIDS
TLDR
Six donors who make a strong CTL response to an immunodominant HLA-B27-restricted epitope and two donors who progressed to AIDS, CTL escape to fixation by the same mutation was observed, but only after 9–12 years of epitope stability.
Tat-specific cytotoxic T lymphocytes select for SIV escape variants during resolution of primary viraemia
TLDR
It is shown that Tat-specific CD8-positive T-lymphocyte responses select for new viral escape variants during the acute phase of infection, and suggests that responses against viral proteins that are expressed early during the viral life cycle might be attractive targets for HIV vaccine development.
Positive selection of HIV-1 cytotoxic T lymphocyte escape variants during primary infection.
TLDR
Positive selection of HIV-1 proviral sequences encoding variants within a CTL epitope in Nef, a gene product critical for viral pathogenicity, is demonstrated during and after seroconversion.
Antiviral pressure exerted by HIV-l-specific cytotoxic T lymphocytes (CTLs) during primary infection demonstrated by rapid selection of CTL escape virus
TLDR
It is shown that in a patient whose early CTL response was focused on a highly immunodominant epitope in gp160, there was rapid elimination of the transmitted virus strain and selection for a virus population bearing amino acid changes at a single residue within this epitope, which conferred escape from recognition by epitope-specific CTL.
Acute phase cytotoxic T lymphocyte escape is a hallmark of simian immunodeficiency virus infection
TLDR
It is shown that viruses from 19 of 21 macaques escaped from CTLs during acute infection and that these escape-selecting C TLs were responsive to lower concentrations of peptide than other SIV-specific CTLS.
Virus-specific cytotoxic T-lymphocyte responses select for amino-acid variation in simian immunodeficiency virus Env and Nef
TLDR
Ten CTL epitopes during the course of simian immunodeficiency virus disease progression in three related macaques showed evidence of positive selection by the time the macaques died, and these findings strongly support the CTL 'escape' hypothesis.
Determinants of HIV-1 Mutational Escape From Cytotoxic T Lymphocytes
TLDR
It is concluded that incomplete viral suppression by CTL can result in rapid emergence of immune escape, but the likelihood is strongly determined by factors influencing the fitness costs of the particular epitope targeted and the ability of responding CTL to recognize specific epitope variants.
Transfer of HIV-1-specific cytotoxic T lymphocytes to an AIDS patient leads to selection for mutant HIV variants and subsequent disease progression
TLDR
It is suggested that active CTL selection of viral variants could contribute to the pathogenesis of AIDS and that clinical progression can occur despite high levels of circulating HIV-1-specific CTLs.
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3
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5
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