Virally mediated inhibition of BAX leukocytes promotes dissemination of murine cytomegalovirus

Mitali Manzur, Peter Fleming, D.C.S. Huang, Mariapia Degli-Esposti, Chris Andoniou

Research output: Contribution to journalArticlepeer-review

32 Citations (Scopus)


The evolutionary survival of viruses relies on their ability to disseminate infectious progeny to sites of transmission. The capacity to subvert apoptosis is thought to be crucial for ensuring efficient viral replication in permissive cells, but its role in viral dissemination in vivo has not been considered. We show here that the murine cytomegalovirus (MCMV) m38.5 protein specifically counters the action of Bax. As predicted from our biochemical data, the capacity of m38.5 to inhibit apoptosis is only apparent in cells unable to activate Bak. Deletion of m38.5 resulted in an attenuated growth of MCMV in vitro. In vivo replication of the Δm38.5 virus was not significantly impaired in visceral organs. However, m38.5 played a central role in protecting leukocytes from Bax-mediated apoptosis, thereby promoting viral dissemination to the salivary glands, the principal site of transmission. These results establish that in vivo MCMV replication induces the activation of Bax in leukocytes, but not other permissive cells, and that MCMV interferes with this process to attain maximum dissemination.
Original languageEnglish
Pages (from-to)312-320
JournalCell Death and Differentiation
Publication statusPublished - 2009


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