A gamma-herpesvirus glycoprotein complex manipulates actin to promote viral spread.
Viruses lack self-propulsion. To move in multi-cellular hosts they must therefore manipulate infected cells. Herpesviruses provide an archetype for many aspects of host manipulation, but only for alpha-herpesviruses in is there much information about they move. Other herpesviruses are not necessarily the same. Here we show that Murine gamma-herpesvirus-68 (MHV-68) induces the outgrowth of long, branched plasma membrane fronds to create an intercellular network for virion traffic. The fronds were actin-based and RhoA-dependent. Time-lapse imaging showed that the infected cell surface became highly motile and that virions moved on the fronds. This plasma membrane remodelling was driven by the cytoplasmic tail of gp48, a MHV-68 glycoprotein previously implicated in intercellular viral spread. The MHV-68 ORF58 was also required, but its role was simply transporting gp48 to the plasma membrane, since a gp48 mutant exported without ORF58 did not require ORF58 to form membrane fronds either. Together, gp48/ORF58 were sufficient to induce fronds in transfected cells, as were the homologous BDLF2/BMRF2 of Epstein-Barr virus. Gp48/ORF58 therefore represents a conserved module by which gamma-herpesviruses rearrange cellular actin to increase intercellular contacts and thereby promote their spread.
Gill
Michael B
MB
Division of Virology, Department of Pathology, University of Cambridge, Cambridge, United Kingdom.
Edgar
Rachel
R
May
Janet S
JS
Stevenson
Philip G
PG
D000199:Actins / Q000502:physiology*; D002460:Cell Line; D006023:Glycoproteins / Q000502:physiology*; D006564:Herpesviridae / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D016366:Open Reading Frames; D014764:Viral Proteins / Q000502:physiology*
D000199:Actins; D006023:Glycoproteins; D014764:Viral Proteins