title: SerpinB2 is an inducible host factor involved in enhancing HIV-1 transcription and replication.
abstract: The serine protease inhibitor SerpinB2 (plasminogen activator inhibitor-2) is a major product of activated monocytes and macrophages and is substantially induced during most inflammatory processes. Distinct from its widely described extracellular role as an inhibitor of urokinase plasminogen activator, SerpinB2 has recently been shown to have an intracellular role as a retinoblastoma protein (Rb)-binding protein that inhibits Rb degradation. Here we show that HIV-1 infection and gp120 treatment of human peripheral blood mononuclear cells resulted in induction of SerpinB2. Furthermore, SerpinB2 expression in THP-1 monocyte/macrophage, Jurkat T, and HeLa cell lines increased replication of HIV-1 and enhanced transcription from the HIV-1 long terminal repeat (LTR) promoter by 3-10-fold. Increased HIV-1 gene expression and transcription was also observed in activated macrophages from SerpinB2+/+ mice compared with macrophages from SerpinB2-/- mice. The SerpinB2-mediated elevation of Rb protein levels appeared to be responsible for enhancing transcription from the core promoter region of the LTR by relieving HDM2-mediated inhibition of Sp1 and/or by increasing the Sp1/Sp3 expression ratios. This is the first report associating HIV-1 replication with SerpinB2 expression and illustrates that SerpinB2 is a potentially important inducible host factor that significantly promotes HIV-1 replication.
authors.affiliation: Queensland Institute of Medical Research, Brisbane, Queensland 4029, Australia.
authors.forename: Grant A
authors.initials: GA
authors.lastname: Darnell
authors.forename: Wayne A
authors.initials: WA
authors.lastname: Schroder
authors.forename: Joy
authors.initials: J
authors.lastname: Gardner
authors.forename: David
authors.initials: D
authors.lastname: Harrich
authors.forename: Hong
authors.initials: H
authors.lastname: Yu
authors.forename: Robert L
authors.initials: RL
authors.lastname: Medcalf
authors.forename: David
authors.initials: D
authors.lastname: Warrilow
authors.forename: Toni M
authors.initials: TM
authors.lastname: Antalis
authors.forename: Secondo
authors.initials: S
authors.lastname: Sonza
authors.forename: Andreas
authors.initials: A
authors.lastname: Suhrbier
mesh_terms: D000818:Animals; D015967:Gene Expression Regulation, Viral; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017396:Plasminogen Activator Inhibitor 2 / Q000378:metabolism / Q000502:physiology*; D011401:Promoter Regions, Genetic; D014779:Virus Replication
chemical_list: D017396:Plasminogen Activator Inhibitor 2