Reciprocal Regulatory Interaction between Human Herpesvirus 8 and Human Immunodeficiency Virus Type 1

Li-Min Huang,Miao-Fen Chao,Mao-Yuan Chen,Hsiu-Ming Shih,Yu-Ping Chiang,Che-Yen Chuang,Chin-Yun Lee

doi:10.1074/jbc.m011314200

Abstract

Human herpesvirus 8 (HHV8) is the primary viral etiologic agent in Kaposi's sarcoma (KS). However, individuals dually infected with both HHV8 and human immunodeficiency virus type 1 (HIV-1) show an enhanced prevalence of KS when compared with those singularly infected with HHV8. Host immune suppression conferred by HIV infection cannot wholly explain this increased presentation of KS. To better understand how HHV8 and HIV-1 might interact directly in the pathogenesis of KS, we queried for potential regulatory interactions between the two viruses. Here, we report that HHV8 and HIV-1 reciprocally up-regulate the gene expression of each other. We found that the KIE2 immediate-early gene product of HHV8 interacted synergistically with Tat in activating expression from the HIV-1 long terminal repeat. On the other hand, HIV-1 encoded Tat and Vpr proteins increased intracellular HHV8-specific expression. These results provide molecular insights correlating coinfection with HHV8 and HIV-1 with an unusually high incidence of KS.

Highlights

Human herpesvirus 8 (HHV8),1 or Kaposi’s sarcoma-associated herpesvirus, is the first human member of ␥2-herpes viruses [1,2,3]
We found that when the HHV8-positive primary effusion lymphoma cell line BCBL-1 [38] was fused to human immunodeficiency virus type 1 (HIV-1)-latent ACH2 cells [39, 40], This paper is available on line at http://www.jbc.org
Because the magnitude of activation by KIE2 alone was less than that observed in the ACH2-BCBL-1 fusion experiments (Fig. 1) we considered whether there could be a synergy between this HHV8 protein and the human immunodeficiency virus (HIV)-1 transactivator, Tat

Summary

Introduction

Human herpesvirus 8 (HHV8),1 or Kaposi’s sarcoma-associated herpesvirus, is the first human member of ␥2-herpes viruses [1,2,3]. We found that the KIE2 immediate-early gene product of HHV8 interacted synergistically with Tat in activating expression from the HIV-1 long terminal repeat. 1 The abbreviations used are: HHV8, human herpesvirus 8; HIV-1 human immunodeficiency virus, type-1; KS, Kaposi’s sarcoma; BCBL, immediate-early; TPA, 12-O-tetradecanoylphorbol-13-acetate; PHA, phytohemagglutinin; IL-6, ilterleukin-6; bp, base pair(s); LTR, long terminal repeat; CMV, cytomegalovirus; RT, reverse transcriptase; PCR, polymerase chain reaction; kb, kilobase(s); ORF, open reading frame; kbp, kilobase pair(s); RPA, RNase protection assay.

Results

Conclusion