B cell-specific expression of Ataxia-telangiectasia mutated protein kinase promotes chronic gammaherpesvirus infection

Eric J. Darrah, Joseph M. Kulinski, Wadzanai P. Mboko, Gang Xin, Laurent P. Malherbe, Stephen B. Gauld, Weiguo Cui, Vera L. Tarakanovaa*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Manipulation of host cellular pathways is a strategy employed by gammaherpesviruses, including mouse gammaherpesvirus 68 (MHV68), in order to negotiate a chronic infection. Ataxia-telangiectasia mutated (ATM) plays a unique yet incompletely understood role in gammaherpesvirus infection, as it has both proviral and antiviral effects. Chronic gammaherpesvirus infection is poorly controlled in a host with global ATM insufficiency, whether the host is a mouse or a human. In contrast, ATM facilitates replication, reactivation, and latency establishment of several gammaherpesviruses in vitro, suggesting that ATM is proviral in the context of infected cell cultures. The proviral role of ATM is also evident in vivo, as myeloidspecific ATM expression facilitates MHV68 reactivation during the establishment of viral latency. In order to better understand the complex relationship between host ATM and gammaherpesvirus infection, we depleted ATM specifically in B cells, a cell type critical for chronic gammaherpesvirus infection. B cell-specific ATM deficiency attenuated the establishment of viral latency due to compromised differentiation of ATM-deficient B cells. Further, we found that during long-term infection, peritoneal B-1b, but not related B-1a, B cells display the highest frequency of gammaherpesvirus infection. While ATM expression did not affect gammaherpesvirus tropism for B-1 B cells, B cell-specific ATM expression was necessary to support viral reactivation from peritoneal cells during long-term infection. Thus, our study reveals a role of ATM as a host factor that promotes chronic gammaherpesvirus infection of B cells.

Original languageEnglish (US)
Article numbere01103-17
JournalJournal of virology
Volume91
Issue number19
DOIs
StatePublished - Oct 1 2017

Keywords

  • ATM
  • B cell
  • Chronic infection
  • Gammaherpesvirus
  • Reactivation
  • T cell response

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Fingerprint

Dive into the research topics of 'B cell-specific expression of Ataxia-telangiectasia mutated protein kinase promotes chronic gammaherpesvirus infection'. Together they form a unique fingerprint.

Cite this