THE EVOLUTIONARY RATE OF NONPATHOGENIC SIMIAN IMMUNODEFICIENCY VIRUS (SIVAGM) IS IN AGREEMENT WITH A RAPID AND CONTINUOUS REPLICATION IN-VIVO

African green monkeys (AGMs) are divided into four species (Cercopithe cus 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 oi 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 (Erythrocebu s patas), in which we could obtain a reproducible and persistent infec tion by SIVagm.tan, As in AGMs, patas monkeys do not develop any disea se 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 selectio n for change reported in pathogenic HIV-1 infections. The rapid accumu lation of mutations observed in AGMs and patas monkeys (0.4-7.2 x 10(- 2) nucleotide substitutions per site per year) suggests a continuous r eplication of SIVagm viruses in vivo. We thus propose that nonpathogen ic SIVagm infections are the result of a long-term selection of SIVagm variants whose dissemination can be controlled in the host, rather th an being explained by a low ability of the virus to replicate in vivo. (C) 1996 Academic Press, Inc.