title: Tumour necrosis factor-alpha stimulates HIV-1 replication in single-cycle infection of human term placental villi fragments in a time, viral dose and envelope dependent manner.
abstract: BACKGROUND
  The placenta plays an important role in the control of in utero HIV-1 mother-to-child transmission (MTCT). Proinflammatory cytokines in the placental environment are particularly implicated in this control. We thus investigated the effect of TNF-alpha on HIV-1 expression in human placental tissues in vitro.
  
  
  RESULTS
  Human placental chorionic villi fragments were infected with varying doses of luciferase reporter HIV-1 pseudotypes with the R5, X4-Env or the vesicular stomatitis virus protein G (VSV-G). Histocultures were then performed in the presence or absence of recombinant human TNF-alpha. Luciferase activity was measured at different time points in cell lysates or on whole fragments using ex vivo imaging systems.A significant increase in viral expression was detected in placental fragments infected with 0.2 ng of p24 antigen/fragment (P = 0.002) of VSV-G pseudotyped HIV-1 in the presence of TNF-alpha seen after 120 hours of culture. A time independent significant increase of viral expression by TNF-alpha was observed with higher doses of VSV-G pseudotyped HIV-1. When placental fragments were infected with R5-Env pseudotyped HIV-1, a low level of HIV expression at 168 hours of culture was detected for 3 of the 5 placentas tested, with no statistically significant enhancement by TNF-alpha. Infection with X4-Env pseudotyped HIV-1 did not lead to any detectable luciferase activity at any time point in the absence or in the presence of TNF-alpha.
  
  
  CONCLUSIONS
  TNF-alpha in the placental environment increases HIV-1 expression and could facilitate MTCT of HIV-1, particularly in an inflammatory context.
authors.affiliation: Laboratory of Virology, Centre Pasteur du Cameroun, Yaoundé, Cameroon. kfutwah@pasteur-yaounde.org
authors.forename: Anfumbom K W
authors.initials: AK
authors.lastname: Kfutwah
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Mary
authors.forename: Marie-Anne
authors.initials: MA
authors.lastname: Nicola
authors.forename: Sandra
authors.initials: S
authors.lastname: Blaise-Boisseau
authors.forename: Françoise
authors.initials: F
authors.lastname: Barré-Sinoussi
authors.forename: Ahidjo
authors.initials: A
authors.lastname: Ayouba
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Menu
mesh_terms: D002824:Chorionic Villi / Q000033:anatomy & histology / Q000378:metabolism / Q000821:virology*; D005260:Female; D017930:Genes, Reporter; D015497:HIV-1 / Q000378:metabolism / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D008156:Luciferases / Q000032:analysis; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology* / Q000502:physiology; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects
chemical_list: C028391:G protein, vesicular stomatitis virus; D008562:Membrane Glycoproteins; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; D014759:Viral Envelope Proteins; D008156:Luciferases