Human TRIM5alpha expression levels and reduced susceptibility to HIV-1 infection

• Published in: The Journal of infectious diseases Vol. 199; no. 11; p. 1657
• Main Authors: Sewram, Shamman, Singh, Ravesh, Kormuth, Emil, Werner, Lise, Mlisana, Koleka, Karim, S S Abdool, Ndung'u, Thumbi
• Format: Journal Article
• Language: English
• Published: United States 01.06.2009
• Subjects: Acquired Immunodeficiency Syndrome - genetics; Acquired Immunodeficiency Syndrome - immunology; Antiviral Restriction Factors; Carrier Proteins - genetics; Gene Expression Regulation; Genetic Predisposition to Disease; HIV Seropositivity - genetics; HIV-1; Humans; Kinetics; Polymerase Chain Reaction; RNA, Messenger - genetics; South Africa; Time Factors; Tripartite Motif Proteins; Ubiquitin-Protein Ligases; Viremia - genetics; South Africa
• ISSN: 0022-1899
• DOI: 10.1086/598861

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.