Human TRIM5α Expression Levels and Reduced Susceptibility to HIV‐1 Infection

Nelson R. Mandela School of Medicine, University of KwaZulu Natal, Durban, South Africa.
The Journal of Infectious Diseases (Impact Factor: 6). 05/2009; 199(11):1657-63. DOI: 10.1086/598861
Source: PubMed


Human TRIM5alpha (TRIM5alphahu), a member of the tripartite motif protein family, displays some anti-human immunodeficiency virus type 1 (HIV-1) activity in vitro, although it is substantially less potent than its rhesus monkey counterpart (TRIM5alpharh). The effects of levels of TRIM5alphahu on prevention or control of HIV-1 infection in vivo are unknown.
We used a quantitative real-time polymerase chain reaction (PCR) assay to measure levels of TRIM5alphahu expression in peripheral blood mononuclear cells (PBMCs) obtained from a cohort of individuals at high risk for HIV-1 infection in Durban, South Africa. Samples were available from 38 infected subjects (with all these samples obtained within 1 year of infection) and from 57 uninfected persons. Matched preinfection and postinfection samples were available from 13 individuals.
TRIM5alphahu messenger RNA levels were lower in the PBMCs of HIV-1-infected subjects than in those of uninfected subjects (P <.001). Seroconverters had lower preinfection levels of TRIM5alphahu than did nonseroconverters (P<.001). TRIM5alphahu levels did not change significantly after infection. There was no correlation between TRIM5alphahu levels and viral loads or CD4(+) T cell counts.
High expression of TRIM5alphahu is associated with reduced susceptibility to HIV-1 infection. Furthermore, infection is not associated with disregulation of TRIM5alphahu. TRIM5alphahu expression levels do not contribute to the control of primary HIV-1 viremia.

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Available from: Salim S Abdool Karim, Jul 01, 2014
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    • "Indeed, although the response to low dose exposure in both vaginal and rectal mucosal lamina propria should be similar, will the vaginal epithelium under strict hormonal control override these events? The data from the CAPRISA study [59] suggest not, but more detailed studies in macaque trials employing vaginal challenge should address this issue. Finally, although we emphasize that the results described in this report are preliminary, they should serve as an important player in guiding future work in the area of the role of lentiviral restriction factors in sexual transmission. "
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    • "Many TRIM proteins are induced by type I and type II IFNs, and several TRIM proteins are known to be required for the restriction of infection by lentiviruses [15]. High TRIM-5α expression induces structural disorder in the retroviral capsid, leading to the interruption of the natural “uncoating” process in a species-specific manner [16], and high expression of TRIM-5α has been associated with reduced susceptibility to HIV-1 infection [17]. TRIM22 blocks the intracellular trafficking of the viral structural protein Gag to the surface of the cell via an IFN-β-dependent mechanism [18]. "
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    • "The tripartite interaction motif 5α (TRIM5) has been recognized to play a role in immunity against retroviral (HIV-1) infection (van Manen et al. 2008; Sewram et al. 2009). Our data provide evidence for associations of polymorphisms in the TRIM5 gene with variations in rubella virus-specific immune responses (TNF-α, GM-CSF and IL-2). "
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