Herpes Simplex Virus 2 Activates Lytic Cycles Replication Of Kaposi's Sarcoma-Associated Herpesvirus And Collaborates With HIV-1 Tat

Patients with acquired immunodeficiency syndrome (AIDS) commonly suffer from opportunistic infections associated with members of the herpes virus family. Kaposi's sarcoma-associated herpesvirus (KSHV) infection appears to be necessary but not enough for Kaposi's sarcoma (KS) development without other cofactors. Previously, we identified that both human herpesvirus 6 and human immunodeficiency virus type 1 Tat were important cofactors that activated lytic cycle replication of KSHV. To investigate whether herpes simplex virus type 2 (HSV-2) influence replication of KSHV and what the role of HIV-1 Tat is in this procedure, HSV-2 strain 333 was used to infect BCBL-1 cell. Production of lytic phase mRNA transcripts, viral proteins and infectious viral particles in BCBL-1 cells were determined with reverse transcription polymerase chain reaction (RT-PCR), real-time quantitative PCR (Real-time PCR) and Western blot. As expected, we showed that HSV-2 was a potentially important factor in the pathogenesis of KS. Compared with control, the mRNA transcription level of ORF50 (switch gene of KSHV cycle replication) was increased 9.92, 2.55, 227, 31.6, 6.6, 75 and 3.02-fold, respectively (P < 0.05) in HSV-2 infected BCBL-1 cells at 3, 6, 12, 24, 48 and 96 h. Similarly, ORF26 (encoding KSHV minor capsid protein) mRNA transcription level was increased from 3 to 96 h, and ORF29 (encoding KSHV package associated protein) mRNA transcription level was increased from 48 to 96 h. The results were further confirmed by a luciferase reporter assay testing ORF50 promoter-driven luciferase activity.Furthermore, we showed that HIV-1 Tat significantly increased the lytic replication of KSHV induced by HSV-2. Compared with corresponding control, ORF26 mRNA level in Tat-transfected BCBL-1 cells infected by HSV-2 was increased 3.92, 1.67, 2.74 and 1.82-fold (P < 0.05) at 6, 24, 48 and 72 h, respectively. The expression level of KSHV vIL-6 was also increased from 6 to 72 h. These findings suggest that HSV-2 may participate in KS pathogenesis by inducing KSHV replication and increasing KSHV viral load. These data also suggest that HSV-2 collaborates with HIV-1 Tat in the pathogenesis of AIDS-related KS patients.