Influence of peak viral load on the extent of CD4+ T-cell depletion in simian HIV infection.
Simian HIV (SHIV) infection of macaques with CXCR4 tropic viruses results in early and profound CD4 T-cell depletion in the first few weeks of infection. Analyzing data from a large study of vaccination and SHIV-89.6P challenge, we observe a strong correlation between peak viral load and the extent of CD4 T-cell depletion in acute infection, consistent with a simple kinetic model of viral infection of CD4 T cells. We have modeled the dynamics of the interaction of virus and CD4 T cells over time to investigate the rate of CD4 T-cell infection and death. This analysis indicates that up to 80% of CD4 T cells are infected at peak viremia and that the proportion of CD4 T cells destroyed is correlated with the peak viral load. The simple relation between viral load and CD4 T-cell depletion allows prediction of the level of viral control required to prevent CD4 T-cell depletion in acute SHIV infection. Whether such a simple relation also holds for HIV or simian immunodeficiency virus infections remains to be determined, particularly in the gut and other anatomic sites in which most early T-cell depletion occurs.
Department of Haematology, Prince of Wales Hospital and Centre for Vascular Research, University of New South Wales, Kensington, New South Wales, Australia.
Miles P
MP
Davenport
Lei
L
Zhang
John W
JW
Shiver
Danilo R
DR
Casmiro
Ruy M
RM
Ribeiro
Alan S
AS
Perelson
D000818:Animals; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000502:physiology / Q000821:virology*; D016923:Cell Death; D006678:HIV / Q000502:physiology*; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D007700:Kinetics; D008251:Macaca; D008433:Mathematics; D008954:Models, Biological; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000502:physiology*; D019562:Viral Load