CD8 + T-cell-mediated control of HIV-1 and SIV infection
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CD8+T-cell-mediated control of HIV-1 and SIV infection Stephanie A. Freel • Kevin O. Saunders Georgia D. Tomaras
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Published online: 19 December 2010 Ó Springer Science+Business Media, LLC 2010
Abstract A detailed understanding of the cellular response to human immunodeficiency virus (HIV-1) infection is needed to inform prevention and therapeutic strategies that aim to contain the AIDS pandemic. The cellular immune response plays a critical role in reducing viral load in HIV-1 infection and in the nonhuman primate model of SIV infection. Much of this virus suppressive activity has been ascribed to CD8?T-cell-directed cytolysis of infected CD4?T cells. However, emerging evidence suggests that CD8?T cells can maintain a lowered viral burden through multiple mechanisms. A thorough understanding of the CD8?T-cell functions in HIV-1 infection that correlate with viral control, the populations responsible for these functions, and the elicitation and maintenance of these responses can provide guidance for vaccine design and potentially the development of new classes of antiretroviral therapies. In this review, we discuss the CD8?T-cell correlates of protection in HIV-1 and SIV infection and recent advances in this field. Keywords Epigenetic
HIV SIV CD8?T-cell Virus inhibition Virus control Vaccine
S. A. Freel Department of Surgery, Duke Human Vaccine Institute, Duke University Medical Center, Rm 113 SORF Building MSRBII, LaSalle St. Ext., Durham, NC 27710, USA K. O. Saunders Department of Molecular Genetics and Microbiology, Duke Human Vaccine Institute, Duke University Medical Center, Rm. 4030 MSRBII, 106 Research Drive, Durham, NC 27710, USA G. D. Tomaras (&) Departments of Surgery, Immunology, Molecular Genetics and Microbiology, Duke Human Vaccine Institute, Duke University Medical Center, Rm. 4079 MSRBII, 106 Research Drive, Durham, NC 27710, USA e-mail: [email protected]
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Immunol Res (2011) 49:135–146
The CD81T-cell response to HIV-1 infection The human immunodeficiency virus (HIV) presents a unique set of challenges to the cellular immune system. The rapidly evolving HIV-1 genome produces an ever-changing milieu of available antigenic epitopes, while targeting cells that play a central role in the cellular immune responses. Thus, the ability of the immune system to respond is impaired. While currently approved therapeutics take advantage of weaknesses in the viral structure and replication cycle, a successful vaccine must rely upon the generation of effective immune responses that are rapidly available and functional at the time of virus challenge. Engaging the most robust cellular response to limit virus replication for those that do become infected will also have a tremendous impact on the HIV-1 epidemic. Because high plasma viral load correlates with risk of HIV-1 transmission, a reduction in virus load by functional CD8?T cells is likely to decrease the number of new HIV-1 infections at the population level. During acute HIV-1 infection, CD8?T-cell responses correlate with the initial dec
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