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Simian immunodeficiency virus types 1 and 2 (SIV mnd 1 and 2) have different pathogenic potentials in rhesus macaques upon experimental cross-species transmission

¹ Laboratoire de Rétrovirologie, Centre International de Recherches Médicales (CIRMF), Franceville, Gabon
² Tulane National Primate Research Center, Covington, LA 70433, USA
³ Centre de Primatologie, Centre International de Recherches Médicales (CIRMF), Franceville, Gabon
⁴ Laboratoire de Virologie, Hôpital St Louis, Paris, France
⁵ Service de Neurovirologie, CEA iMETI, 92265 Fontenay aux Roses, France

Correspondence
Sandrine Souquière
souquiere{at}cirmf.org

sandsouquiere{at}yahoo.fr

The mandrill (Mandrillus sphinx) is naturally infected by two types of simian immunodeficiency virus (SIV): SIVmnd types 1 and 2. Both of these viruses cause long-term, non-progressive infections in their natural host despite high plasma viral loads. This study assessed the susceptibility of rhesus macaques to infection by these two types of SIVmnd and compared the virological and basic immunological characteristics of the resulting infections with those observed in natural infection in mandrills. Whilst both SIVmnd types induced similar levels of virus replication during acute infection in both mandrills and macaques, they produced a more pronounced CD4⁺ T-cell depletion in rhesus macaques that persisted longer during the initial stage of infection. Pro-inflammatory cytokine responses were also induced at higher levels in rhesus macaques early in the infection. During the chronic phase of infection in mandrills, which in this case was followed for up to 2 years after infection, high levels of chronic virus replication did not induce significant changes in CD4⁺ or CD8⁺ T-cell counts. In rhesus macaques, the overall chronic virus replication level was lower than in mandrills. At the end of the follow-up period, although the viral loads of SIVmnd-1 and SIVmnd-2 were relatively similar in rhesus macaques, only SIVmnd-1-infected rhesus macaques showed significant CD4⁺ T-cell depletion, in the context of higher levels of CD4⁺ and CD8⁺ T-cell activation, compared with SIVmnd-infected mandrills. The demonstration of the ability of both SIVmnd types to induce persistent infections in rhesus macaques calls for a careful assessment of the potential of these two viruses to emerge as new human pathogens.