Expression Analysis of LEDGF/p75, APOBEC3G, TRIM5alpha, and Tetherin in a Senegalese Cohort of HIV-1-Exposed Seronegative Individuals
Background: HIV-1 replication depends on a delicate balance between cellular co-factors and antiviral restriction factors.
Lens epithelium-derived growth factor (LEDGF/p75) benefits HIV, whereas apolipoprotein B mRNA-editing catalytic
polypeptide-like 3G (APOBEC3G), tripartite motif 5alpha (TRIM5a), and tetherin exert anti-HIV activity. Expression levels of
these proteins possibly contribute to HIV-1 resistance in HIV-1-exposed populations.
Methodology/Principal Findings: We used real-time PCR and flow cytometry to study mRNA and protein levels respectively
in PBMC and PBMC subsets. We observed significantly reduced LEDGF/p75 protein levels in CD4+ lymphocytes of HIV-1-
exposed seronegative subjects relative to healthy controls, whereas we found no differences in APOBEC3G, TRIM5a, or
tetherin expression. Untreated HIV-1-infected patients generally expressed higher mRNA and protein levels than healthy
controls. Increased tetherin levels, in particular, correlated with markers of disease progression: directly with the viral load
and T cell activation and inversely with the CD4 count.
Conclusions/Significance: Our data suggest that reduced LEDGF/p75 levels may play a role in resistance to HIV-1 infection,
while increased tetherin levels could be a marker of advanced HIV disease. Host factors that influence HIV-1 infection and
disease could be important targets for new antiviral therapies.
Auteur(s) : Mous K, Jennes W, Camara M, Seydi M, Daneau D, Mboup S, Kestens L, Van Ostade X
Pages : e33934
Année de publication : 2012
Revue : PLoS ONE
N° de volume : 07
Type : Article
Mise en ligne par : CAMARA Makhtar