ORF18 is a transfactor that is essential for late gene transcription of a gammaherpesvirus.
Lytic replication of the tumor-associated human gammaherpesviruses Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus has important implications in pathogenesis and tumorigenesis. Herpesvirus lytic genes have been temporally classified as exhibiting immediate-early (IE), early, and late expression kinetics. Though the regulation of IE and early gene expression has been studied extensively, very little is known regarding the regulation of late gene expression. Late genes, which primarily encode virion structural proteins, require viral DNA replication for their expression. We have identified a murine gammaherpesvirus 68 (MHV-68) early lytic gene, ORF18, essential for viral replication. ORF18 is conserved in both beta- and gammaherpesviruses. By generating an MHV-68 ORF18-null virus, we characterized the stage of the virus lytic cascade that requires the function of ORF18. Gene expression profiling and quantitation of viral DNA synthesis of the ORF18-null virus revealed that the expression of early genes and viral DNA replication were not affected; however, the transcription of late genes was abolished. Hence, we have identified a gammaherpesvirus-encoded factor essential for the expression of late genes independently of viral DNA synthesis.
Arumugaswami
Vaithilingaraja
V
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, 23-120 Center for Health Sciences, Los Angeles, CA 90095-1735, USA.
Wu
Ting-Ting
TT
Martinez-Guzman
DeeAnn
D
Jia
Qingmei
Q
Deng
Hongyu
H
Reyes
Nichole
N
Sun
Ren
R
D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D017124:Conserved Sequence; D006224:Cricetinae; D018142:Gammaherpesvirinae / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D020869:Gene Expression Profiling; D015967:Gene Expression Regulation, Viral; D016679:Genome, Viral / Q000235:genetics; D006801:Humans; D007700:Kinetics; D051379:Mice; D008969:Molecular Sequence Data; D016366:Open Reading Frames / Q000235:genetics*; D010957:Plasmids / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D011995:Recombination, Genetic / Q000235:genetics; D016415:Sequence Alignment; D013997:Time Factors; D014158:Transcription, Genetic / Q000235:genetics*; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication
D000941:Antigens; D014764:Viral Proteins