Reactivation of Kaposi's sarcoma-associated herpesvirus infection from latency by expression of the ORF 50 transactivator, a homolog of the EBV R protein.
Kaposi's sarcoma (KS)-associated herpesvirus (KSHV), or human herpesvirus 8, is a lymphotropic virus strongly linked to several AIDS-related neoplasms. The primary reservoir of infection consists of latently infected B lymphocytes and possibly other mononuclear cells. Viral reactivation from latency and spread from this lymphoid reservoir is presumably required for development of nonlymphoid tumors like KS. Here we show that deregulated expression of a single viral gene, ORF 50, which encodes a transactivator able to selectively upregulate delayed-early viral genes, suffices to disrupt latency and induce the lytic gene cascade in latently infected B cells. The identification of this gene opens the way to studies of the physiologic mechanisms controlling reactvation of KSHV from latency.
Lukac
D M
DM
Howard Hughes Medical Institute and Departments of Microbiology and Medicine, University of California, San Francisco, California, 94143, USA.
Renne
R
R
Kirshner
J R
JR
Ganem
D
D
D001402:B-Lymphocytes / Q000821:virology; D015967:Gene Expression Regulation, Viral; D004854:Herpesvirus 4, Human / Q000235:genetics; D019288:Herpesvirus 8, Human / Q000235:genetics / Q000502:physiology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics; D011401:Promoter Regions, Genetic; D012514:Sarcoma, Kaposi / Q000503:physiopathology* / Q000821:virology; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic; D014764:Viral Proteins; D014775:Virus Activation; D017735:Virus Latency
C068382:BRLF1 protein, Human herpesvirus 4; D017874:Immediate-Early Proteins; C116742:ORF 50 transactivator; D015534:Trans-Activators; D014157:Transcription Factors; D014764:Viral Proteins