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The SIV Envelope Glycoprotein, Viral Tropism, and Pathogenesis: Novel Insights from Nonhuman Primate Models of AIDS

[ Vol. 16 , Issue. 1 ]

Author(s):

Adrienne E. Swanstrom, Gregory Q. Del Prete, Claire Deleage, Samra E. Elser, Andrew A. Lackner and James A. Hoxie*   Pages 29 - 40 ( 12 )

Abstract:


Background: Cellular tropism of human immunodeficiency virus (HIV-1) is closely linked to interactions between the viral envelope glycoprotein (Env) with CD4 and chemokine receptor family members, CCR5 and CXCR4. This interaction plays a key role in determining anatomic sites that are infected in vivo and the cascade of early and late events that result in chronic immune activation, immunosuppression and ultimately, AIDS. CD4+ T cells are critical to adaptive immune responses, and their early and rapid infection in gut lamina propria and secondary lymphoid tissues in susceptible hosts likely contributes to viral persistence and progression to disease. CD4+ macrophages are also infected, although their role in HIV-1 pathogenesis is more controversial.

Methods: Pathogenic infection by simian immunodeficiency viruses (SIV) in Asian macaques as models of HIV-1 infection has enabled the impact of cellular tropism on pathogenesis to be directly probed. This review will highlight examples in which experimental interventions during SIV infection or the introduction of viral mutations have altered cellular tropism and, subsequently, pathogenesis.

Results: Alterations to the interaction of Env and its cellular receptors has been shown to result in changes to CD4 dependence, coreceptor specificity, and viral tropism for gut CD4+ T cells and macrophages.

Conclusion: Collectively, these findings have yielded novel insights into the critical role of the viral Env and tropism as a driver of pathogenesis and host control and have helped to identify new areas for targeted interventions in therapy and prevention of HIV-1 infection.

Keywords:

Tropism, pathogenesis, SIV, CD4, CXCR4, CCR5, macrophage, CD4-independence.

Affiliation:

AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc., Frederick, MD, AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc., Frederick, MD, AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc., Frederick, MD, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, Tulane National Primate Research Center, Covington, LA, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA

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