Highly selective escape from KSHV-mediated host mRNA shutoff and its implications for viral pathogenesis

TitleHighly selective escape from KSHV-mediated host mRNA shutoff and its implications for viral pathogenesis
Publication TypeJournal Article
Year of Publication2004
AuthorsGlaunsinger B, Ganem D
JournalThe Journal of experimental medicine
Volume200
Issue3
Pagination391-8
Date Published2004 Aug 2
ISSN0022-1007
KeywordsDNA-Binding Proteins, Gene Expression Profiling, Gene Expression Regulation, Herpesvirus 8, Human, Humans, Hypoxia-Inducible Factor 1, Hypoxia-Inducible Factor 1, alpha Subunit, Interleukin-6, Nuclear Proteins, Oligonucleotide Array Sequence Analysis, Receptors, Chemokine, RNA, Messenger, Transcription Factors
AbstractDuring Kaposi's sarcoma (KS)-associated herpesvirus (KSHV) lytic infection, many virus-encoded signaling molecules (e.g., viral G protein-coupled receptor [vGPCR]) are produced that can induce host gene expression in transiently transfected cells, and roles for such induced host genes have been posited in KS pathogenesis. However, we have recently found that host gene expression is strongly inhibited by 10-12 h after lytic reactivation of KSHV, raising the question of whether and to what extent de novo host gene expression induced by viral signaling molecules can proceed during the lytic cycle. Here, we show by microarray analysis that expression of most vGPCR target genes is drastically curtailed by this host shutoff. However, rare cellular genes can escape the host shutoff and are potently up-regulated during lytic KSHV growth. Prominent among these is human interleukin-6, whose striking induction may contribute to the overexpression of this cytokine in several disease states linked to KSHV infection.
DOI10.1084/jem.20031881
Alternate JournalJ. Exp. Med.