Kaposi's sarcoma-associated herpesvirus reduces cellular myeloid differentiation primaryresponse gene 88 (MyD88) expression via modulation of its RNA

Amy Lingel, Erica Ehlers, Qianli Wang, Mingxia Cao, Charles Wood, Rongtuan Lin, Luwen Zhang

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Kaposi's sarcoma (KS)-associated herpesvirus (KSHV) is a human gammaherpesvirus associated with several human malignancies. The replication and transcription activator (RTA) is necessary and sufficient for the switch from KSHV latency to lytic replication. Interleukin 1 (IL-1) is a major mediator for inflammation and plays an important role in both innate and adaptive immunity. Myeloid differentiation primary response gene 88 (MyD88) is an essential adaptor molecule for IL-1 as well as most Toll-like receptor signaling. In this study, we identified a novel mechanism by which KSHV interferes with host inflammation and immunity. KSHV RTA specifically reduces the steady-state protein levels of MyD88, and physiological levels of MyD88 are downregulated during KSHV lytic replication when RTA is expressed. The N-terminal region of RTA is required for the reduction of MyD88. Additional studies demonstrated that RTA targets MyD88 expression at the RNA level, inhibits RNA synthesis of MyD88, and may bind MyD88 RNA. Finally, RTA inhibits IL-1-mediated activation of NF-κB. Because IL-1 is abundant in the KS microenvironment and inhibits KSHV replication, this work may expand our understanding of how KSHV evades host inflammation and immunity for its survival in vivo.

Original languageEnglish (US)
Pages (from-to)180-188
Number of pages9
JournalJournal of virology
Volume90
Issue number1
DOIs
StatePublished - Jan 1 2016

Fingerprint

Human herpesvirus 8
Human Herpesvirus 8
Herpesviridae
transcription (genetics)
interleukin-1
RNA
Interleukin-1
Genes
genes
inflammation
Immunity
immunity
Myeloid Differentiation Factor 88
Inflammation
Inflammation Mediators
Kaposi's Sarcoma
Toll-Like Receptors
sarcoma
Adaptive Immunity
Innate Immunity

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Kaposi's sarcoma-associated herpesvirus reduces cellular myeloid differentiation primaryresponse gene 88 (MyD88) expression via modulation of its RNA. / Lingel, Amy; Ehlers, Erica; Wang, Qianli; Cao, Mingxia; Wood, Charles; Lin, Rongtuan; Zhang, Luwen.

In: Journal of virology, Vol. 90, No. 1, 01.01.2016, p. 180-188.

Research output: Contribution to journalArticle

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