title: Expression analysis of LEDGF/p75, APOBEC3G, TRIM5alpha, and tetherin in a Senegalese cohort of HIV-1-exposed seronegative individuals.
abstract: 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 (TRIM5α), and tetherin exert anti-HIV activity. Expression levels of these proteins possibly contribute to HIV-1 resistance in HIV-1-exposed populations.
  
  
  RESULTS
  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, TRIM5α, 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
  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.
authors.affiliation: Laboratory for Proteinscience, Proteomics and Epigenetic Signaling, Department of Biomedical Sciences, University of Antwerp, Wilrijk, Belgium.
authors.forename: Kim
authors.initials: K
authors.lastname: Mous
authors.forename: Wim
authors.initials: W
authors.lastname: Jennes
authors.forename: Makhtar
authors.initials: M
authors.lastname: Camara
authors.forename: Moussa
authors.initials: M
authors.lastname: Seydi
authors.forename: Géraldine
authors.initials: G
authors.lastname: Daneau
authors.forename: Souleymane
authors.initials: S
authors.lastname: Mboup
authors.forename: Luc
authors.initials: L
authors.lastname: Kestens
authors.forename: Xaveer
authors.initials: X
authors.lastname: Van Ostade
mesh_terms: D000071480:APOBEC-3G Deaminase; D000328:Adult; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism*; D004781:Environmental Exposure; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D015658:HIV Infections / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D018023:HIV Seronegativity / Q000502:physiology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012675:Senegal; D013601:T-Lymphocytes / Q000378:metabolism; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases; D000074010:Bone Marrow Stromal Antigen 2
chemical_list: D000071480:APOBEC-3G Deaminase; D015703:Antigens, CD; D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins; D003564:Cytidine Deaminase; D058851:GPI-Linked Proteins; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2; C119380:lens epithelium-derived growth factor; C477346:TRIM5 protein, human; C464924:APOBEC3G protein, human