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.
Highlights
At least 40 primate species in Africa are infected by diverse simian immunodeficiency viruses (SIVs) assigned to six major phylogenetic lineages; the mosaic nature of the SIV genomes attests to the common simian-to-simian transmission of SIVs [1,2]
Sequences representing actively replicating SIV were amplified directly from virion RNA in the plasma by RT-PCR. 29 V1V2 and 7 gag clone sequences analyzed using maximum parsimony, neighborjoining (NJ), and maximum likelihood (ML) phylogenetic tree constructions demonstrated that the source inoculum (SI) was phylogenetically distinct from commonly used laboratory SIV isolates (Figure S1)
The range of pairwise nucleotide diversity calculated for the SI population was 0.3%–5.1% for V1V2 and 0.7%-4.6% for gag
Summary
At least 40 primate species in Africa are infected by diverse simian immunodeficiency viruses (SIVs) assigned to six major phylogenetic lineages; the mosaic nature of the SIV genomes attests to the common simian-to-simian transmission of SIVs [1,2] These African nonhuman primate reservoir hosts maintain normal CD4 T cell counts and avoid AIDS, despite lifelong SIV infection [3,4,5,6]. Considerable V1V2 amino acid length variation and high and variable numbers of glycosylation consensus sequences are observed This high diversity of SIV V1V2 in the natural host environment may promote the potential for crossspecies transmission by generating the env variants necessary to ensure successful infection of new hosts
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