TRIM5α and TRIM22 are differentially regulated according to HIV-1 infection phase and compartment.
| dc.contributor.author | Singh, Ravesh. | |
| dc.contributor.author | Patel, Vinod B. | |
| dc.contributor.author | Mureithi, Marianne W. | |
| dc.contributor.author | Naranbhai, Vivek. | |
| dc.contributor.author | Ramsuran, Duran. | |
| dc.contributor.author | Tulsi, Sahil. | |
| dc.contributor.author | Hiramen, Keshni. | |
| dc.contributor.author | Werner, Lise. | |
| dc.contributor.author | Mlisana, Koleka Patience. | |
| dc.contributor.author | Altfeld, Marcus. | |
| dc.contributor.author | Luban, Jeremy. | |
| dc.contributor.author | Kasprowicz, Victoria. | |
| dc.contributor.author | Dheda, Keertan. | |
| dc.contributor.author | Abdool Karim, Salim Safurdeen. | |
| dc.contributor.author | Ndung'u, Peter Thumbi. | |
| dc.date.accessioned | 2016-10-27T10:07:40Z | |
| dc.date.available | 2016-10-27T10:07:40Z | |
| dc.date.created | 2014 | |
| dc.date.issued | 2014 | |
| dc.description | CAPRISA, 2014. | en_US |
| dc.description.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. | en_US |
| dc.identifier.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. | en_US |
| dc.identifier.uri | http://dx.doi.org/10.1128/JVI.03603-13 | en_US |
| dc.identifier.uri | http://hdl.handle.net/10413/13549 | |
| dc.language.iso | en | en_US |
| dc.publisher | American Society for Microbiology. | en_US |
| dc.subject | TRIM5α. | en_US |
| dc.subject | TRIM22. | en_US |
| dc.subject | HIV-1 infection. | en_US |
| dc.title | TRIM5α and TRIM22 are differentially regulated according to HIV-1 infection phase and compartment. | en_US |
| dc.type | Peer reviewed journal article | en_US |