TY - JOUR
T1 - TRIM5α and TRIM22 are differentially regulated according to hiv-1 infection phase and compartment
AU - Singh, Ravesh
AU - Patel, Vinod
AU - Mureithi, Marianne W.
AU - Naranbhai, Vivek
AU - Ramsuran, Duran
AU - Tulsi, Sahil
AU - Hiramen, Keshni
AU - Werner, Lise
AU - Mlisana, Koleka
AU - Altfeld, Marcus
AU - Luban, Jeremy
AU - Kasprowicz, Victoria
AU - Dheda, Keertan
AU - Abdool Karim, Salim S.
AU - Ndung'u, Thumbi
PY - 2014/4
Y1 - 2014/4
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84896961890&partnerID=8YFLogxK
U2 - 10.1128/JVI.03603-13
DO - 10.1128/JVI.03603-13
M3 - Article
C2 - 24478420
AN - SCOPUS:84896961890
SN - 0022-538X
VL - 88
SP - 4291
EP - 4303
JO - Journal of Virology
JF - Journal of Virology
IS - 8
ER -