Abstract
Pathogenic human immunodeficiency virus (HIV)/Simian immunodeficiency virus (SIV) infection is associated with increased T-cell apoptosis. In marked contrast to HIV infection in humans and SIV infection in macaques, the SIV infection of natural host species is typically nonpathogenic despite high levels of viral replication. In these nonpathogenic primate models, no observation of T-cell apoptosis was observed, suggesting that either SIV is less capable of directly inducing apoptosis in natural hosts (likely as a result of coevolution/coadaptation with the host) or, alternatively, that the indirect T-cell apoptosis plays the key role in determining the HIV-associated T-cell depletion and progression to acquired immune deficiency syndrome (AIDS). Understanding the molecular and cellular mechanisms responsible for the disease-free equilibrium in natural hosts for SIV infection, including those determining the absence of high levels of T-cell apoptosis, is likely to provide important clues regarding the mechanisms of AIDS pathogenesis in humans.
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Abbreviations
- HIV:
-
human immunodeficiency virus
- SIV:
-
Simian immunodeficiency virus
- SHIV:
-
Simian-human immunodeficiency virus
- AIDS:
-
acquired immune deficiency syndrome
- NHPs:
-
African non-human primates
- SMs:
-
sooty mangabeys
- AGMs:
-
African green monkeys
- LNs:
-
lymph nodes
- FDC:
-
follicular dendritic cells
- HAART:
-
highly active antiretroviral therapy
- DISC:
-
death-inducing signaling complex
- zVAD-fmk:
-
z-Val-Ala-Asp-fmk.
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Acknowledgements
This work was funded by grants from the Agence Nationale de Recherche sur le Sida (ANRS) to JE and MMT, and by NIH Grants R01-AI52775 and R21-AI54234 to GS. FP was supported by a postdoctoral fellowship from Ensemble Contre le Sida (ECS) and DA was supported by a postdoctoral fellowship from Fondation recherche Médicale (FRM).
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This work is dedicated to the memory of Bruno Hurtrel
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Hurtrel, B., Petit, F., Arnoult, D. et al. Apoptosis in SIV infection. Cell Death Differ 12 (Suppl 1), 979–990 (2005). https://doi.org/10.1038/sj.cdd.4401600
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DOI: https://doi.org/10.1038/sj.cdd.4401600
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