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Updated: May 21, 2026
Analysis of Simian Immunodeficiency Virus-specific CD8+ T-cells in Rhesus Macaques by Peptide-MHC-I Tetramer Staining
Published on: December 23, 2016
Electrostatic potential of human immunodeficiency virus type 2 and rhesus macaque simian immunodeficiency virus
Katarzyna Bozek1, Emi E Nakayama, Ken Kono
1Max Planck Institute for Informatics Saarbrücken, Germany.
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.
Insights
Human immunodeficiency virus type 2 (HIV-2) and simian immunodeficiency virus (SIV) exhibit different sensitivities to TRIM5α, a host restriction factor. Differences in capsid protein electrostatic potential, particularly on the L4/5 loop, explain this varying TRIM5α restriction between HIV-2 and SIVmac.
Area of Science:
- Virology
- Molecular Biology
- Immunology
Background:
- Human immunodeficiency virus type 2 (HIV-2) and simian immunodeficiency virus (SIV) share genomic similarities but differ in their susceptibility to TRIM5α, a retroviral restriction factor.
- HIV-2 replication is restricted by rhesus (Rh) TRIM5α, whereas SIVmac strain 239 (SIVmac239) is not, with viral capsid protein identified as the key determinant.
Purpose of the Study:
- To investigate the molecular determinants of differential TRIM5α sensitivity between HIV-2 and SIVmac.
- To analyze the electrostatic potential on the capsid protein interaction surfaces of HIV-2 strain GH123 and SIVmac239.
Main Methods:
- Comparative analysis of capsid protein sequences between HIV-2 GH123 and SIVmac239.
- Investigation of electrostatic potential distribution on the surface of the L4/5 loop of both viral capsid proteins.
Main Results:
- Despite high amino acid identity (>87%), HIV-2 GH123 capsid protein exhibits a predominantly positive electrostatic potential on the L4/5 loop.
- SIVmac239 capsid protein displays a predominantly negative electrostatic potential on the same L4/5 loop surface.
- The L4/5 loop is a critical determinant for Rh TRIM5α sensitivity.
Conclusions:
- The distinct electrostatic surface charge distribution on the L4/5 loop of HIV-2 GH123 and SIVmac239 capsid proteins likely underlies their differential sensitivity to rhesus TRIM5α.
- This suggests that the TRIM5α binding site may possess charge complementarity to the HIV-2 GH123 capsid surface.
