Human cytomegalovirus cell-to-cell spread in the absence of an essential assembly protein

Maria C. Silva, Jörg Schröer, Thomas Shenk

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

The human cytomegalovirus UL99-coded pp28 is a myristoylated phosphoprotein located in the virion tegument domain, which resides between the capsid and envelope. A previous study has demonstrated that BADsubUL99, a pp28-deficient mutant virus, fails to assemble enveloped virus particles. Capsids, coated with tegument proteins, accumulate in the cytoplasm of mutant virus-infected cells. This phenotype indicates that pp28 is required for the acquisition of an envelope; it presumably acts by directing tegument-associated capsids to bud through an intracellular membrane derived from the cell's secretory apparatus that has been modified to contain viral transmembrane glycoproteins. Here we demonstrate that BADsubUL99 can spread from cell to cell, even though highly sensitive assays fail to detect infectious virus progeny in cultures of infected fibroblasts. We propose that, in the absence of pp28, tegument-coated capsids might nevertheless bud through cellular membranes, including the plasma membrane. If this suggestion is correct, the enveloped particle could potentially infect an adjacent cell to mediate the cell-to-cell spread that is observed. This mode of spread might also occur after infection with wild-type virus, and it could facilitate immune evasion, assuming that the resulting particles do not have a normal complement of virus-coded envelope glycoproteins.

Original languageEnglish (US)
Pages (from-to)2081-2086
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number6
DOIs
StatePublished - Feb 8 2005

All Science Journal Classification (ASJC) codes

  • General

Keywords

  • Mutant cytomegalovirus
  • Spread from cell to cell
  • Virus assembly

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