Viral Protein Regulatory Of Human Immunodeficiency Virus Type 1 Regulates The Lytic Cycle Replication Of Kaposi's Sarcoma-associated Herpesvirus

Human immunodeficiency virus type 1 (HIV-1) infection can significantly increase the risk of Kaposi's sarcoma (KS) occurrence in individuals infected with Kaposi's sarcoma-associated herpesvirus (KSHV). KSHV infection is necessary but not sufficient for KS development without other cofactors. Previously, we determined that HIV-1 transactivative transcription protein (Tat) was one of the cofactors that activated lytic cycle replication of KSHV. Here, we further demonstrated that HIV-1 viral protein regulatory (Vpr) was a potentially important factor in the pathogenesis of KS. After successful construction and later expression of the recombinant plasmid of Vpr in the eukaryotic cells, it was transiently transfected into BCBL-1 and BC-3 cells. Real-time quantitative polymerase chain reaction (real-time PCR) showed that the mRNA transcription levels of ORF50 (switch gene of KSHV cycle replication), ORF26 (encoding KSHV minor capsid protein) in Vpr-transfected BCBL-1 cells were significantly decreased, respectively, compared with the corresponding control. Besides, reverse transcription polymerase chain reaction (RT-PCR) also showed that Vpr down-regulated the lytic mRNA transcription levels in BCBL-1 and BC-3 cells. Moreover, overexpression of Vpr in BCBL-1 cells down-regulated expression of viral interleukin 6 (vIL-6) by using Western blot analysis. Luciferase assays indicated that Vpr inhibited KSHV replication by directly down-regulating the activity of ORF50 promoter. These findings suggest that, in AIDS-related KS (AIDS-KS) patients, Vpr may participate in the immune escape by inhibiting KSHV lytic replication in KS pathogenesis.