The Evolutionary Rate of Nonpathogenic Simian Immunodeficiency Virus (SIVagm) Is in Agreement with a Rapid and Continuous Replicationin Vivo

Abstract

African green monkeys (AGMs) are divided into four species (Cercopithecus aethiops, C. pygerythrus, C. sabaeus, C. tantalus), each harboring a species-specific simian immunodeficiency virus (SIVagm). Little is known about the host and/or viral factors that are responsible for the apathogenicity of SIVagm infections in their natural hosts. In order to analyze the specific selective pressures exerted by the host on the virus in vivo, we compared the genetic evolution of SIVagm.tan in its natural host (C. tantalus) and in a foreign host species (Erythrocebus patas), in which we could obtain a reproducible and persistent infection by SIVagm.tan. As in AGMs, patas monkeys do not develop any disease following SIVagm infection. Our longitudinal study in env (V3-C3-V4-C4-V5) of SIVagm.tan from three AGMs and three patas monkeys revealed a high ratio of synonymous to nonsynonymous mutation frequencies (1.5-6.2). These data indicate that the selective pressures for stability exerted by AGMs and patas monkeys on SIVagm override positive selection for change reported in pathogenic HIV-1 infections. The rapid accumulation of mutations observed in AGMs and patas monkeys (0.4-7.2 x 10(-2) nucleotide substitutions per site per year) suggests a continuous replication of SIVagm viruses in vivo. We thus propose that nonpathogenic SIVagm infections are the result of a long-term selection of SIVagm variants whose dissemination can be controlled in the host, rather than being explained by a low ability of the virus to replicate in vivo.

Wide Range of Viral Load in Healthy African Green Monkeys Naturally Infected with Simian Immunodeficiency Virus

“…As confirmation that this virus has not changed in pathogenesis by passage in macaques, experimental infection of SIV-seronegative AGM with this pathogenic isolate does not result in disease (20). Quantitative studies of viral loads in naturally infected AGM revealed that the proviral load in peripheral blood mononuclear cells (PBMC) and lymph nodes of such animals is similar to that observed during asymptomatic infection of humans with HIV-1 (8,19), and viral populations in infected AGM appear to undergo significant evolution (34). The purpose of the present study was to characterize the virus load and distribution in tissues and blood of healthy AGM of the vervet species (C. pygerythrus) that were naturally infected with SIVagm.…”

“…SIV-infected African monkeys such as sooty mangabeys infected with SIVsm or AGM infected with SIVagm exhibit no evidence of immunodeficiency (3,7,8,13,16,20,21,34,36,37,42). However, experimental infection of Asian species of monkeys (Macaca sp.)…”

“…Similar to the species-specific virulence of SIVsm in sooty mangabeys and macaques, AGM infected with SIVagm remain asymptomatic (3,7,8,13,19,20,21,34,35,37) whereas experimental transmission of virus to pigtailed (PT) macaques (Macaca nemestrina) can result in an AIDS-like syndrome (20). As confirmation that this virus has not changed in pathogenesis by passage in macaques, experimental infection of SIV-seronegative AGM with this pathogenic isolate does not result in disease (20).…”

Impact of Viral Factors on Very Early In Vivo Replication Profiles in Simian Immunodeficiency Virus SIVagm-Infected African Green Monkeys

“…During the chronic phase of infection, plasma vRNA levels show a wide range in naturally SIVagm-infected AGMs. Some AGMs have low VLs (below 10 3 copies/ml plasma), whereas in others, viral replication during the chronic phase is high (3.5 ϫ 10 6 to 1.1 ϫ 10 7 RNA copies/ml) (9,18,22,51). Thus, viral replication in AGMs reproduces situations observed in pathogenic infections (9,18,22).…”

Évolution et virulence des lentivirus de primates

“…De plus, l'équi-libre évolutif hôte-virus paraît stable. La population virale ne subit pas de fortes contraintes chez les hôtes simiens naturels en situation non pathogène : une grande diversité et une grande taille des populations virales, reflets des charges virales élevées, s'accompagnent de faibles pressions immunologiques en faveur du changement [22,23]. …”