New research on gut CD4 T-cell depletion and HIV pathogenesis

Richard Jefferys, TAG

In both HIV and SIV infections, it has been shown that the most rapid and extensive loss of CD4 T cells occurs in the gut.

As a consequence, a theory has emerged positing that gut CD4 T-cell depletion plays a central causative role in driving HIV pathogenesis; the proposed mechanism is that gut wall integrity becomes compromised, leading to the leakage of normally friendly bacteria from the digestive tract and into systemic circulation, which in turn contributes to persistent immune activation and, ultimately, progression to AIDS.

However, some scientists have remained skeptical of this theory, suggesting instead that gut CD4 T-cell depletion is an effect of HIV infection, but not necessarily the primary cause of disease progression. The skeptics have gained some support from studies showing that severe gut CD4 T-cell depletion occurs during acute SIV infection in monkey species that experience no apparent ill effects from the virus (sooty mangabeys and African green monkeys). [1]

A paper published recently in the Journal of Virology now shows that the opposite phenomenon is also possible: a modified SIV that does not cause loss of gut CD4 T cells nevertheless causes persistent immune activation and progression to simian AIDS in rhesus macaques. [2]


TAG Basic Science Blog, New research on gut CD4 T-cell depletion and HIV pathogenesis. (31 December 2013).


  1. Jefferys R. Gut CD4 T cell Depletion: Mucosal Catastrophe or Minor Disruption? TAG Basic Science Blog. (22 August 2007).
  2. Breed M et al. Loss of a Tyrosine-Dependent Trafficking Motif in the SIV Envelope Cytoplasmic Tail Spares Mucosal CD4 Cells but Does Not Prevent Disease Progression. Published ahead of print, 14 November 2012, doi: 10.1128/JVI.01928-12.

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