title: Herpes simplex virus type 2 triggers reactivation of Kaposi's sarcoma-associated herpesvirus from latency and collaborates with HIV-1 Tat.
abstract: Kaposi's sarcoma-associated herpesvirus (KSHV) infection was necessary but not sufficient for Kaposi's sarcoma (KS) development without other cofactors. Previously, we identified that both human immunodeficiency type 1 (HIV-1) Tat and herpes simplex virus 1 (HSV-1) were important cofactors reactivating KSHV from latency. Here, we further investigated the potential of herpes simplex virus 2 (HSV-2) to influence KSHV replication and examined the role of Tat in this procedure. We demonstrated that HSV-2 was a potentially important factor in the pathogenesis of KS, as determined by production of lytic phase mRNA transcripts, viral proteins and infectious viral particles in BCBL-1 cells. These results were further confirmed by an RNA interference experiment using small interfering RNA targeting KSHV Rta and a luciferase reporter assay testing Rta promoter-driven luciferase activity. Mechanistic studies showed that HSV-2 infection activated nuclear factor-kappa B (NF-κB) signaling pathway. Inhibition of NF-κB pathway enhanced HSV-2-mediated KSHV activation, whereas activation of NF-κB pathway suppressed KSHV replication in HSV-2-infected BCBL-1 cells. Additionally, ectopic expression of Tat enhanced HSV-2-induced KSHV replication. These novel findings suggest a role of HSV-2 in the pathogenesis of KS and provide the first laboratory evidence that Tat may participate HSV-2-mediated KSHV activation, implying the complicated pathogenesis of acquired immunodeficiency syndrome (AIDS)-related KS (AIDS-KS) patients.
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Tang
authors.forename: Di
authors.initials: D
authors.lastname: Qin
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Lv
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Zhu
authors.forename: Xinting
authors.initials: X
authors.lastname: Ma
authors.forename: Qin
authors.initials: Q
authors.lastname: Yan
authors.forename: Yi
authors.initials: Y
authors.lastname: Zeng
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Guo
authors.forename: Ninghan
authors.initials: N
authors.lastname: Feng
authors.forename: Chun
authors.initials: C
authors.lastname: Lu
mesh_terms: D018258:Herpesvirus 2, Human / Q000502:physiology*; D019288:Herpesvirus 8, Human / Q000502:physiology*; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D012514:Sarcoma, Kaposi / Q000209:etiology / Q000821:virology; D014775:Virus Activation; D017735:Virus Latency; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000502:physiology*
chemical_list: D016328:NF-kappa B; D054322:tat Gene Products, Human Immunodeficiency Virus