SIVsm Quasispecies Adaptation to a New Simian Host

Open Access
Publisher Website
Google Scholar
Abstract
Despite the potential for infectious agents harbored by other species to become emerging human pathogens, little is known about why some agents establish successful cross-species transmission, while others do not. The simian immunodeficiency viruses (SIVs), certain variants of which gave rise to the human HIV-1 and HIV-2 epidemics, have demonstrated tremendous success in infecting new host species, both simian and human. SIVsm from sooty mangabeys appears to have infected humans on several occasions, and was readily transmitted to nonnatural Asian macaque species, providing animal models of AIDS. Here we describe the first in-depth analysis of the tremendous SIVsm quasispecies sequence variation harbored by individual sooty mangabeys, and how this diverse quasispecies adapts to two different host species—new nonnatural rhesus macaque hosts and natural sooty mangabey hosts. Viral adaptation to rhesus macaques was associated with the immediate amplification of a phylogenetically related subset of envelope (env) variants. These variants contained a shorter variable region 1 loop and lacked two specific glycosylation sites, which may be selected for during acute infection. In contrast, transfer of SIVsm to its natural host did not subject the quasispecies to any significant selective pressures or bottleneck. After 100 d postinfection, variants more closely representative of the source inoculum reemerged in the macaques. This study describes an approach for elucidating how pathogens adapt to new host species, and highlights the particular importance of SIVsm env diversity in enabling cross-species transmission. The replicative advantage of a subset of SIVsm variants in macaques may be related to features of target cells or receptors that are specific to the new host environment, and may involve CD4-independent engagement of a viral coreceptor conserved among primates. Why do some infectious agents establish successful cross-species transmission while others do not? Despite the clear potential for diseases harbored by animals to become emerging human pathogens, this question remains unanswered. Certain simian immunodeficiency viruses (SIVs) responsible for the human HIV-1 and HIV-2 epidemics have succeeded in infecting new host species, including humans. This study provides clues to how an SIV adapts to a new host in an experimental cross-species transmission. Indeed, many emerging diseases are caused by highly mutation-prone RNA viruses like SIV, which exist not as a single species, but rather as a population of genetic variants within a single infection. The presence of numerous viral variants in an infected animal increases the chance that variants with the ability to enter into or multiply in a new host species are present. This study describes how an SIV population from a natural reservoir host, the sooty mangabey, adapts to a new monkey species, the rhesus macaque. A limited subset of SIV variants containing unique viral surface proteins appears well suited to multiply in the new host. This study documents how viral variation facilitates cross-species transmission, and highlights the particular importance of immunodeficiency virus envelope variants in infecting new hosts.