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

MC Silva, J Schröer, T Shenk - Proceedings of the National …, 2005 - National Acad Sciences
MC Silva, J Schröer, T Shenk
Proceedings of the National Academy of Sciences, 2005National Acad Sciences
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 BAD sub UL99, 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 …
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.
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