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: Qiao Tang, Di Qin, Zhigang Lv, Xiaolei Zhu, Xinting Ma, Qin Yan, Yi Zeng, Yuanyuan Guo, Ninghan Feng, Chun Lu
• Journal: PloS one (PLoS One) Vol. 7 Issue 2 Pg. e31652 ( 2012) ISSN: 1932-6203 [Electronic] United States
• PMID: 22347501 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• NF-kappa B
• tat Gene Products, Human Immunodeficiency Virus

Topics

• Herpesvirus 2, Human (physiology)
• Herpesvirus 8, Human (physiology)
• Humans
• NF-kappa B (metabolism)
• Sarcoma, Kaposi (etiology, virology)
• Virus Activation
• Virus Latency
• tat Gene Products, Human Immunodeficiency Virus (physiology)