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Author Notes:

Address correspondence to Mirko Paiardini, Email: mirko.paiardini@emory.edu

C.S.M. and B.C. equally contributed.

We thank all the animal care and veterinary staff at the Yerkes National Primate Research Center as well as the Virology Core of the Emory Center for AIDS Research (CFAR).

We also thank Thomas Vanderford and Aftab Ansari for critical readings of the manuscript.

Finally, we thank the Cleveland Immunopathogenesis Consortium (BBC/CLIC) for advice and helpful discussions.

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.


Research Funding:

Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award numbers R01AI084836 and R56AI087186 to M.P. and R37 AI066998 to G.S. as well as by grants OD011132 (to the Yerkes National Primate Research Center) and P30AI50409 (to the Emory Center for AIDS Research).

M.P.D. is supported by the National Health and Medical Research Council (Australia).


  • Science & Technology
  • Life Sciences & Biomedicine
  • Virology

Increased Stability and Limited Proliferation of CD4(+) Central Memory T Cells Differentiate Nonprogressive Simian Immunodeficiency Virus (SIV) Infection of Sooty Mangabeys from Progressive SIV Infection of Rhesus Macaques


Journal Title:

Journal of Virology


Volume 88, Number 8


, Pages 4533-4542

Type of Work:

Article | Final Publisher PDF


Depletion of CD4+ central memory T (TCM) cells dictates the tempo of progression to AIDS in simian immunodeficiency virus (SIV)-infected rhesus macaques (RMs) both in the natural history of infection and in the context of vaccination. CD4+ TCM cells of sooty mangabeys (SMs), a natural host for SIV in which infection is nonpathogenic, are less susceptible to SIV infection than CD4+ TCM cells of RMs. Whether this relative protection from infection translates into increased stability of CD4+ TCM cells in natural versus nonnatural hosts has not yet been determined. Here we compared, both cross-sectionally and longitudinally, the levels of CD4+ TCM cells in a large cohort of SMs and RMs and the association between CD4+ TCM levels and the main virologic and immunologic markers of disease progression. Consistent with their lower susceptibility to infection, CD4+ TCM cells of SIV-infected SMs are lost with kinetics 20 times slower than those of SIV-infected RMs. Remarkably, the estimated length of time of SIV infection needed for CD4+ TCM cells to fall to half of their initial levels is <16 months for RMs but >17 years for SMs. Furthermore, the fraction of proliferating CD4+ TCM cells is significantly lower in SIV-infected SMs than in SIV-infected RMs, and the extent of CD4+ TCM cell proliferation is associated positively with CD4+ T cell levels in SIV-infected SMs but negatively with CD4+ T cell levels in SIV-infected RMs. Collectively, these findings identify increased stability and maintenance of the prohomeostatic role of CD4+ TCM cells as features distinguishing nonprogressive from progressive SIV infections and support the hypothesis of a direct mechanistic link between the loss of CD4+ TCM cells and disease progression.

Copyright information:

© 2014, American Society for Microbiology.

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