Cellular v-ATPase is required for virion assembly compartment formation in human cytomegalovirus infection

Jonathan Pavelin, Dominique McCormick, Stephen Chiweshe, Saranya Ramachandran, Yao-Tang Lin, Finn Grey

Research output: Contribution to journalArticlepeer-review

Abstract

Successful generation of virions from infected cells is a complex process requiring orchestrated regulation of host and viral genes. Cells infected with human cytomegalovirus (HCMV) undergo a dramatic reorganization of membrane organelles resulting in the formation of the virion assembly compartment, a process that is not fully understood. Here we show that acidification of vacuoles by the cellular v-ATPase is a crucial step in the formation of the virion assembly compartment and disruption of acidification results in mis-localization of virion components and a profound reduction in infectious virus levels. In addition, knockdown of ATP6V0C blocks the increase in nuclear size, normally associated with HCMV infection. Inhibition of the v-ATPase does not affect intracellular levels of viral DNA synthesis or gene expression, consistent with a defect in assembly and egress. These studies identify a novel host factor involved in virion production and a potential target for antiviral therapy.

Original languageEnglish
Article number160298
JournalOpen Biology
Volume7
Issue number11
DOIs
Publication statusPublished - 30 Nov 2017

Keywords

  • human cytomegalovirus,
  • v-ATPase
  • assembly and egress
  • herpesvirus
  • host virus interaction

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