Background:  The reasons for the lack of disease following simian immunodeficiency virus (SIV) infection in African non-human primates are not known. We previously reported a markedly lower expression of CCR5 expression on the CD4 T cells from blood, lymph nodes, and intestine in the natural hosts. The aim of this study was therefore to determine whether this results in lower CD4⁺ T cell depletion in the intestine in African green monkeys, as a mechanism of protection against disease progression.

Methods:  We infected 6 Caribbean African green monkeys and 4 rhesus macaques  with SIV_agm.sab92018. Monkeys were followed 490 days post-infection. Plasma viral loads (VL) were determined by real-time polymerase chain reaction (PCR). The dynamics of CD4⁺, CD8⁺, and CD20 cells, and T cell activation were followed in blood, lymph nodes, and intestine by flow-cytometry.

Results:  SIV_agm.sab replicated at high levels during primary infection of Carribean African green monkeys, with peak VL of 10⁷ to 10⁸ copies/mL occurring by day 8 to 10 post-infection. Afterward, a decrease in plasma VL resulted in set-point values as high as 2x10⁵ copies/ml, reached by day 42 post-infection and maintained through day 490 post-infection. CD4⁺ counts in the blood showed a transitory depletion at the peak of VL, then CD4⁺ T cells reached normal levels in the chronic phase of SIV_agm.sab infection. In striking contrast, a dramatic CD4⁺ T cell decrease was observed in the African green monkey gut that was maintained until day 490 post-infection. Rhesus macaques infected with SIV_agm.sab had peak VL as high as 10⁹ copies/mL and then they controlled the infection. The undetectable VL levels were reached by day 72 post-infection. An important depletion of CD4⁺ T cells was also seen in the intestine of rhesus monkeys. Then, concomitant with the control of VL, a partial immune restoration occurred in rhesus monkeys, with CD4⁺ T cells reaching around half of the preinfection levels by day 490.

Conclusions:  Our study demonstrates that, as in rhesus macaques, in natural hosts of SIV, CD4⁺ T cell depletion occurs preferentially in the gastrointestinal tract. We therefore show for the first time that a massive CD4⁺ T cell depletion during primary infection at the main site of lentiviral infection does not necessarily result in progressive infection and that in natural hosts of SIV, this depletion has no significant pathogenic consequences. In hosts controlling chronic SIV infection, such as rhesus macaques infected with SIV_agm, the immune restoration in the intestine is only partial. These data call for further investigation of the mechanisms controlling the deleterious effects of SIV in both hosts.