Onanga et al. conclude:
"Altogether, our data show that SIVmnd-1 is well adapted to mandrills.
This study extends the concept that high viral load alone is not
sufficient for disease progression. We showed that in SIVmnd-1-infected
mandrills, CD4+ and CD8+ levels in both blood and LNs are stable during
the first year. These data suggest a lower general state of activation
of the immune system in vivo early on. The investigation of the factors
associated with the balance between the virus and the host should
provide valuable explanations for understanding the progressive loss of
CD4+ cell function in HIV-infected humans and/or the discrepancies
between virological and immunological responses observed in about 20% of
patients undergoing highly active antiretroviral therapy. Understanding
the factors which are responsible for maintaining the steady state of
infection in African primates should provide help in elaborating
valuable immunostrategies against AIDS."
--------------------------
Journal of Virology, October 1, 2002, p. 10256-10263, Vol. 76, No. 20
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 in Mandrillus
sphinx
Richard Onanga,1 Christopher Kornfeld,2 Ivona Pandrea,1, Jerome
Estaquier,3 Sandrine Souquiere,1 Pierre Rouquet,4 Virginie
Poaty Mavoungou,1 Olivier Bourry,4 Souleymane M'Boup,5 Françoise
Barre-Sinoussi,2 François Simon,1,6 Cristian Apetrei,1, Pierre
Roques,1,7* and Michaela C. Müller-Trutwin2 E-mail: pro...@pasteur.fr.
Departement de Virologie,1 Centre de Primatologie, Centre International
de Recherches Médicales, Franceville, Gabon,4 Unite de Biologie des
Rétrovirus, Institut Pasteur,2 INSERM EMI 9922, Hôpital Bichat-Claude
Bernard, Paris VII, Paris,3 Laboratoire de Virologie, Faculte de
Médecine, Centre Hospitalier Charles Nicolle, Rouen,6 Service de
Neurovirologie, CEA, Fontenay aux Roses, France,7 Universite Cheikh Anta
Diop, Dakar, Senegal5 E-mail: pro...@pasteur.fr.
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 x 106 to 2 x 108 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 x 105 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.