The exonuclease and host shutoff functions of the SOX protein of Kaposi's sarcoma-associated herpesvirus are genetically separable

TitleThe exonuclease and host shutoff functions of the SOX protein of Kaposi's sarcoma-associated herpesvirus are genetically separable
Publication TypeJournal Article
Year of Publication2005
AuthorsGlaunsinger B, Chavez L, Ganem D
JournalJournal of virology
Volume79
Issue12
Pagination7396-401
Date Published2005 Jun
ISSN0022-538X
KeywordsCell Line, Exonucleases, Gene Expression Regulation, Herpesvirus 8, Human, Humans, Mutation, Open Reading Frames, Ribonucleases, RNA, Messenger, Subcellular Fractions, Viral Proteins
AbstractThe Kaposi's sarcoma-associated herpesvirus (KSHV) SOX protein, encoded by ORF37, promotes shutoff of host cell gene expression during lytic viral replication by dramatically impairing mRNA accumulation. SOX is the KSHV homolog of the alkaline exonuclease of other herpesviruses, which has been shown to function as a DNase involved in processing and packaging the viral genome. Although the exonuclease activity of these proteins is widely conserved across all herpesviruses, the host shutoff activity observed for KSHV SOX is not. We show here that SOX expression sharply reduces the half-life of target mRNAs. Extensive mutational analysis reveals that the DNase and host shutoff activities of SOX are genetically separable. Lesions affecting the DNase activity cluster in conserved regions of the protein, but residues critical for mRNA degradation are not conserved across the viral family. Additionally, we present evidence suggesting that the two different functions of SOX occur within distinct cellular compartments-DNase activity in the nucleus and host shutoff activity in the cytoplasm.
DOI10.1128/JVI.79.12.7396-7401.2005
Alternate JournalJ. Virol.