TRIM5α and TRIM22 are differentially regulated according to HIV-1 infection phase and compartment.
Loading...
Date
2014
Journal Title
Journal ISSN
Volume Title
Publisher
American Society for Microbiology.
Abstract
The antiviral role of TRIM E3 ligases in vivo is not fully understood. To test the hypothesis that TRIM5α and TRIM22 have differential transcriptional regulation and distinct anti-HIV roles according to infection phase and compartment, we measured TRIM5α, TRIM22, and type I interferon (IFN-I)-inducible myxovirus resistance protein A (MxA) levels in peripheral blood mononuclear cells (PBMCs) during primary and chronic HIV-1 infection, with chronic infection samples being matched PBMCs and central nervous system (CNS)-derived cells. Associations with biomarkers of disease progression were explored. The impact of IFN-I, select proinflammatory cytokines, and HIV on TRIM E3 ligase-specific expression was investigated. PBMCs from individuals with primary and chronic HIV-1 infection had significantly higher levels of MxA and TRIM22 than did PBMCs from HIV-1-negative individuals (P < 0.05 for all comparisons). PBMCs from chronic infection had lower levels of TRIM5α than did PBMCs from primary infection or HIV-1-uninfected PBMCs (P = 0.0001 for both). In matched CNS-derived samples and PBMCs, higher levels of MxA (P = 0.001) and TRIM5α (P = 0.0001) in the CNS were noted. There was a negative correlation between TRIM22 levels in PBMCs and plasma viral load (r = -0.40; P = 0.04). In vitro, IFN-I and, rarely, proinflammatory cytokines induced TRIM5α and TRIM22 in a cell type-dependent manner, and the knockdown of either protein in CD4(+) lymphocytes resulted in increased HIV-1 infection. These data suggest that there are infection-phase-specific and anatomically compartmentalized differences in TRIM5α and TRIM22 regulation involving primarily IFN-I and specific cell types and indicate subtle differences in the antiviral roles and transcriptional regulation of TRIM E3 ligases in vivo.
Description
CAPRISA, 2014.
Keywords
TRIM5α., TRIM22., HIV-1 infection.
Citation
Singh, R., Patel, V., Mureithi, M.W., Naranbhai, V., Ramsuran, D., Tulsi, S., Hiramen, K., Werner, L., Mlisana, K., Altfeld, M., Luban, J., Kasprowicz V., Dheda K., Abdool Karim S. S. and Ndung'u T. 2014. TRIM5α and TRIM22 are differentially regulated according to HIV-1 infection phase and compartment. Journal of virology 88(8), 4291-4303.