High Levels of Viral Replication Contrast with Only Transient Changes in CD4⁺and CD8⁺Cell Numbers during the Early Phase of Experimental Infection with Simian Immunodeficiency Virus SIVmnd-1 inMandrillus sphinx

Abstract

Early events during human immunodeficiency virus infections are considered to reflect the capacity of the host to control infection. We have studied early virus and host parameters during the early phase of simian immunodeficiency virus SIVmnd-1 nonpathogenic infection in its natural host, Mandrillus sphinx. Four mandrills were experimentally infected with a primary SIVmnd-1 strain derived from a naturally infected mandrill. Two noninfected control animals were monitored in parallel. Blood and lymph nodes were collected at three time points before infection, twice a week during the first month, and at days 60, 180, and 360 postinfection (p.i.). Anti-SIVmnd-1 antibodies were detected starting from days 28 to 32 p.i. Neither elevated temperature nor increased lymph node size were observed. The viral load in plasma peaked between days 7 to 10 p.i. (2 ؋ 10 6 to 2 ؋ 10 8 RNA equivalents/ml). Viremia then decreased 10-to 1,000-fold, reaching the viral set point between days 30 to 60 p.i. The levels during the chronic phase of infection were similar to that in the naturally infected donor mandrill (2 ؋ 10 5 RNA equivalents/ml). The CD4 ؉ cell numbers and percentages in blood and lymph nodes decreased slightly (<10%) during primary infection, and CD8؉ cell numbers increased transiently. All values returned to preinfection infection levels by day 30 p.i. CD8؉ cell numbers or percentages, in peripheral blood and lymph nodes, did not increase during the 1 year of follow-up. In conclusion, SIVmnd-1 has the capacity for rapid and extensive replication in mandrills. Despite high levels of viremia, CD4؉ and CD8؉ cell numbers remained stable in the post-acute phase of infection, raising questions regarding the susceptibility of mandrill T cells to activation and/or cell death in response to SIVmnd-1 infection in vivo.

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

“…Previously, we demonstrated that the pathogenic potential of SIVmnd-1 in mandrills is not different from that of other species-specific SIVs (Muller & Barré-Sinoussi, 2003;Pandrea et al, 2006;Silvestri et al, 2003) and we reported that there was no pathogenic difference between SIVmnd-1 and SIVmnd-2 in mandrills (Onanga et al, 2002. In the present study, we first confirmed these findings and showed again, although in a limited number of mandrills, that there was no discernible difference in biological or clinical outcome between SIVmnd-1 and SIVmnd-2.…”

“…The viral inocula used consisted of plasma obtained directly from acutely infected mandrills at peak viraemia following experimental SIVmnd types 1 and 2 infection of rhesus macaques infection, to avoid potential problems due to virus selection through in vitro culture, as described previously (Onanga et al, 2002. Mandrills 2I and 5A4 and rhesus macaques 93057, 93183A and P9110A were inoculated with 500 ml plasma containing 7.5610 6 RNA copies of SIVmnd-1 (strains 16C and 12A3) (Pandrea et al, 2008a).…”

“…Although SIVmnd-1 and SIVmnd-2 have different origins, these two viruses have identical virological characteristics in their natural hosts (Onanga et al, 2002. Thus, during experimental infection, high peak viral loads (VLs) and high levels of chronic virus replication are associated with only transient decreases in peripheral CD4 + T-cell counts.…”

“…To date, more than 40 different SIVs have been described and they infect different African species of monkeys and apes at high levels of prevalence Hahn et al, 2000;VandeWoude & Apetrei, 2006). Unlike pathogenic human immunodeficiency virus (HIV) in humans and SIV in macaques, natural SIV infections generally do not progress to acquired immune deficiency syndrome (AIDS) (Chakrabarti, 2004;Hirsch, 2004;Muller & Barré-Sinoussi, 2003;Norley et al, 1999;Onanga et al, 2002Onanga et al, , 2006Pandrea et al, 2008b;Silvestri, 2005). In fact, only a handful of cases of immunodeficiency have been described to date in African NHP species, all of which have occurred in captive animals (Ling et al, 2004;Pandrea et al, 2001;Traina-Dorge et al, 1992).…”

“…All rhesus macaques were male: 93057 (8 years old), 93183A (3 years old), P9110A (6 years old), 93036 (8 years old), 93183B (3 years old) and 93046A (6 years old). All animal protocols and procedures were approved by the Gabonese Ethics Committee for Animal Experimentation.The viral inocula used consisted of plasma obtained directly from acutely infected mandrills at peak viraemia following experimental infection, to avoid potential problems due to virus selection through in vitro culture, as described previously (Onanga et al, 2002. Mandrills 2I and 5A4 and rhesus macaques 93057, 93183A and P9110A were inoculated with 500 ml plasma containing 7.5610 6 RNA copies of SIVmnd-1 (strains 16C and 12A3) (Pandrea et al, 2008a).…”