Abstract
Human immunodeficiency virus type 2 (HIV-2) and simian immunodeficiency virus isolated from a macaque monkey (SIVmac) are assumed to have originated from simian immunodeficiency virus isolated from sooty mangabey (SIVsm). Despite their close similarity in genome structure, HIV-2 and SIVmac show different sensitivities to TRIM5α, a host restriction factor against retroviruses. The replication of HIV-2 strains is potently restricted by rhesus (Rh) monkey TRIM5α, while that of SIVmac strain 239 (SIVmac239) is not. Viral capsid protein is the determinant of this differential sensitivity to TRIM5α, as the HIV-2 mutant carrying SIVmac239 capsid protein evaded Rh TRIM5α-mediated restriction. However, the molecular determinants of this restriction mechanism are unknown. Electrostatic potential on the protein-binding site is one of the properties regulating protein–protein interactions. In this study, we investigated the electrostatic potential on the interaction surface of capsid protein of HIV-2 strain GH123 and SIVmac239. Although HIV-2 GH123 and SIVmac239 capsid proteins share more than 87% amino acid identity, we observed a large difference between the two molecules with the HIV-2 GH123 molecule having predominantly positive and SIVmac239 predominantly negative electrostatic potential on the surface of the loop between α-helices 4 and 5 (L4/5). As L4/5 is one of the major determinants of Rh TRIM5α sensitivity of these viruses, the present results suggest that the binding site of the Rh TRIM5α may show complementarity to the HIV-2 GH123 capsid surface charge distribution.
Highlights
The host range of human immunodeficiency virus type 1 (HIV-1) is narrow, limited to humans and chimpanzees (Gao et al, 1999)
THE 3-D STRUCTURAL MODELS OF Human immunodeficiency virus type 2 (HIV-2) GH123 AND SIVmac239 capsid protein (CA) N-TERMINAL DOMAINS Previously, we evaluated the sensitivity of HIV-2 GH123 and SIVmac239 to Rh and CM TRIM5αs, and found that HIV-2 GH123 was sensitive to CM and Rh TRIM5αs (Song et al, 2007; Kono et al, 2008; Figure 1A)
We observed a large difference between the HIV-2 GH123 and SIVmac239 CA N-terminal domains, with the HIV-2 GH123 molecule having predominantly positive and SIVmac239 predominantly negative electrostatic potential on the surface of loop between α-helices 4 and 5 (L4/5)
Summary
The host range of human immunodeficiency virus type 1 (HIV-1) is narrow, limited to humans and chimpanzees (Gao et al, 1999). HIV-1 fails to replicate in activated CD4-positive T lymphocytes from Old World monkeys (OWM), such as rhesus (Rh; Shibata et al, 1995; Himathongkham and Luciw, 1996) and cynomolgus (CM) monkeys (Akari et al, 1996, 1999). Human immunodeficiency virus type 2 (HIV-2) is assumed to have originated from SIVsm as the result of zoonotic events involving monkeys and humans (Hahn et al, 2000). Previous studies have shown that HIV-2 strains vary widely in their ability to grow in cells of OWM (Castro et al, 1990, 1991; Locher et al, 1998, 2003; Fujita et al, 2003)
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