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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Sewram
Shamman
S
Nelson R. Mandela School of Medicine, University of KwaZulu Natal, Durban, South Africa.
Singh
Ravesh
R
Kormuth
Emil
E
Werner
Lise
L
Mlisana
Koleka
K
Karim
S S Abdool
SS
Ndung'u
Thumbi
T
D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics* / Q000276:immunology; D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins / Q000235:genetics*; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006679:HIV Seropositivity / Q000235:genetics; D015497:HIV-1; D006801:Humans; D007700:Kinetics; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D013019:South Africa; D013997:Time Factors; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases; D014766:Viremia / Q000235:genetics*
D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins; D012333:RNA, Messenger; D000070584:Tripartite Motif Proteins; C477346:TRIM5 protein, human; D044767:Ubiquitin-Protein Ligases