Glycoprotein L disruption reveals two functional forms of the murine gammaherpesvirus 68 glycoprotein H.
The herpesvirus glycoprotein H (gH) and gL associate to form a heterodimer that plays a central role in virus-driven membrane fusion. When archetypal alpha- or betaherpesviruses lack gL, gH misfolds and progeny virions are noninfectious. In order to define the role that gL plays in gamma-2 herpesvirus infections, we disrupted its coding sequence in murine gammaherpesvirus-68 (MHV-68). MHV-68 lacking gL folded gH into a conformation antigenically distinct from the form that normally predominates on infected cells. gL-deficient virions bound less well than the wild type to epithelial cells and fibroblasts. However, they still incorporated gH and remained infectious. The cell-to-cell spread of gL-deficient viruses was remarkably normal, as was infection, dissemination, and latency establishment in vivo. Viral membrane fusion was therefore gL independent. The major function of gL appeared to be allowing gH to participate in cell binding prior to membrane fusion. This function was most important for the entry of MHV-68 virions into fibroblasts and epithelial cells.
Gillet
Laurent
L
Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, United Kingdom.
May
Janet S
JS
Colaco
Susanna
S
Stevenson
Philip G
PG
D000818:Animals; D000911:Antibodies, Monoclonal; D002460:Cell Line; D006224:Cricetinae; D005260:Female; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D018144:Rhadinovirus / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D014760:Viral Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014771:Virion / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D017735:Virus Latency / Q000235:genetics
D000911:Antibodies, Monoclonal; D008562:Membrane Glycoproteins; D014760:Viral Fusion Proteins