483 Early Extensive Viremia During SIVmnd-2 Infection in mandrillus sphinx is Associated with Transient Activation of Peripheral and Lymphnode T-cells R Onanga*1, S Souquière1, M Makuwa1, F Simon2, F Barré-Sinoussi3, M C Müller-Trutwin3, P Roques1 1Ctr Intl de Res Med de Franceville, Gabon; 2Univ de Rouen, France; and 3Inst Pasteur, Paris, France
Background: The non-pathogenic nature of SIV infection in African non-human primates may be the result of co-evolution of the virus with its respective host. Conversely, cross-transmitted viruses can show increased pathogenicity, as observed for SIVsm/SIVmac in macaques. Mandrills are infected by 2 types of viruses SIVmnd-1 and SIVmnd-2 which seems the seems to be the result of ancient cross-transmission events. We observed high viral replication in contrast to only transient Changes in CD4+ and CD8+ cell numbers during the early phase of SIVmnd-1 experimental infection. As early virus-host interactions predict the level of viral control and disease progression in HIV-1 infected humans, we investigated the dynamics of SIVmnd-2 primary infection in mandrills to compare SIVmnd replication with HIV-1 and HIV-2 infection.
Methods: SIVmnd-2 virus was obtained from its original living host which was asymptomatic PG13. Four (4) monkeys were inoculated intravenously with 1.34 x 108 copies of SIVmnd-2/ml plasma of this wild-type. Animals were bled at days -30, -15, 0, 7, 10, 14, 21, 28, 66, 90, and 121 for serological investigations, Real Time PCR quantification of viral RNA dynamics, and dynamics of CD28, CD45RA, CD3+ CD4+ and CD3+ CD8+ lymphocyte subsets in peripheral blood and lymph nodes.
Results: During the early phase of non-pathogenic SIVmnd-2 infection in its natural host species, the mandrill, we have observed high plasma viremia (108 – 107 RNA copies/ml) between days 7 and 10. Then, we detected a decline in virus replication until the chronic phase steady state at 106 – 105 RNA copies/ml. We observed a transient decline of CD3+CD4+ cells in the blood in animals displaying high viremia. We also detected signs for activation of CD4+ and CD8+ cells in blood as well as in LNs upon SIVmnd-2 infection between days 5 to 17 post infection surrounding the peak of viral replication. The extent of changes of CD4+ and CD8+ in CD3+ and CD28+ cell populations was associated with the level of viremia. Anti-gp36 and anti-V3 antibodies were detected starting from days 28-32. Activation markers on T-cells thereafter returned to pre-infection values despite continuous viremia (105 to 106 RNA copies/ml).
Conclusions: Our data thus reveal that primary infection SIVmnd-2 in mandrill is quite similar to the primary infection of SIVmnd-1 and suggests that SIVmnd-2 is adapted to its host.
