Abstract
HIV-1 exhibits a narrow host range, hindering the development of a robust animal model of pathogenesis. Past studies have demonstrated that the restricted host range of HIV-1 may be largely due to the inability of the virus to antagonize and evade effector molecules of the interferon response in other species. They have also guided the engineering of HIV-1 clones that can replicate in CD4 T-cells of Asian macaque species. However, while replication of these viruses in macaque hosts is persistent, it has been limited and without progression to AIDS. In a new study, Hatziioannou et al., demonstrate for the first time that adapted macaque-tropic HIV-1 can persistently replicate at high levels in pigtailed macaques (Macaca nemestrina), but only if CD8 T-cells are depleted at the time of inoculation. The infection causes rapid disease and recapitulates several aspects of AIDS in humans. Additionally, the virus undergoes genetic changes to further escape innate immunity in association with disease progression. Here, the importance of these findings is discussed, as they relate to pathogenesis and model development.
Highlights
Primate lentiviruses are highly adapted to replication in their native hosts but have limited capacity to infect and spread to new species [1]
Apolipoprotein B mRNA-editing, enzyme-catalytic, polypeptide-like 3G (APOBEC3G), tetherin (BST-2 or CD317), tripartite motif-containing protein 5α (TRIM5α), and TRIM5-cyclophilin A (TRIMcyp) fusion proteins interfere with replication at different stages of the viral life cycle [2,3,4,5,6]
As an alternative way to test this hypothesis, several groups have engineered HIV-1 to be resistant to restriction factors of Asian macaque species, examined replication in CD4 T-cells of these species, and challenged the respective hosts to determine if the “macaque-tropic” viruses could establish persistent infection and cause AIDS
Summary
Primate lentiviruses are highly adapted to replication in their native hosts but have limited capacity to infect and spread to new species [1]. The species-specific tropism of primate lentiviruses correlates with evasion of TRIM5α or functional activity of the viral antagonists against APOBEC3G or tetherin [7,8,9,10,11,12,13]. These data suggest that innate immunity is a formidable defense against the transmission of lentiviruses into new species
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