Onset of human cytomegalovirus replication in fibroblasts requires the presence of an intact vimentin cytoskeleton.
Like all viruses, herpesviruses extensively interact with the host cytoskeleton during entry. While microtubules and microfilaments appear to facilitate viral capsid transport toward the nucleus, evidence for a role of intermediate filaments in herpesvirus entry is lacking. Here, we examined the function of vimentin intermediate filaments in fibroblasts during the initial phase of infection of two genotypically distinct strains of human cytomegalovirus (CMV), one with narrow (AD169) and one with broad (TB40/E) cell tropism. Chemical disruption of the vimentin network with acrylamide, intermediate filament bundling in cells from a patient with giant axonal neuropathy, and absence of vimentin in fibroblasts from vimentin(-/-) mice severely reduced entry of either strain. In vimentin null cells, viral particles remained in the cytoplasm longer than in vimentin(+/+) cells. TB40/E infection was consistently slower than that of AD169 and was more negatively affected by the disruption or absence of vimentin. These findings demonstrate that an intact vimentin network is required for CMV infection onset, that intermediate filaments may function during viral entry to facilitate capsid trafficking and/or docking to the nuclear envelope, and that maintenance of a broader cell tropism is associated with a higher degree of dependence on the vimentin cytoskeleton.
Miller
Matthew S
MS
Department of Microbiology and Immunology, Health Sciences Addition HSA 320, The University of Western Ontario, London, Ontario, Canada.
Hertel
Laura
L
D000818:Animals; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000235:genetics / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D003599:Cytoskeleton / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D005347:Fibroblasts / Q000378:metabolism* / Q000821:virology; D006801:Humans; D007382:Intermediate Filaments / Q000378:metabolism / Q000821:virology; D051379:Mice; D014746:Vimentin / Q000235:genetics / Q000378:metabolism*; D053586:Virus Internalization; D014779:Virus Replication
D014746:Vimentin