A role for human cytomegalovirus glycoprotein O (gO) in cell fusion and a new hypervariable locus.
A cell fusion assay using fusion-from-without (FFWO) recombinant adenoviruses (RAds) and specific antibody showed a role in fusion modulation for glycoprotein gO, the recently identified third component of the gH/gL gCIII complex of human cytomegalovirus (HCMV). As in HCMV, RAd gO expressed multiple glycosylated species with a mature product of 125 kDa. Coexpression with gH/gL RAds showed gCIII reconstitution in the absence of other HCMV products and stabilisation by intermolecular disulfide bonds. Properties of HCMV clinical isolate, Pt, also implicated gO in cell spread. Compared to laboratory strain AD169, Pt was resistant to gH antibody plaque inhibition, but mature gH was identical. However, the gO sequences were highly divergent (20%), with further variation in laboratory strain Towne gO (34%). Thus, gO forms gCIII with gH/gL, performs in cell fusion, and is a newly identified HCMV hypervariable locus which may influence gCIII's function in mediating infection.
Paterson
David A
DA
Pathogen Molecular Biology and Biochemistry Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, University of London, Keppel Street, London WC1E 7HT, United Kingdom.
Dyer
Angela P
AP
Milne
Richard S B
RS
Sevilla-Reyes
Edgar
E
Gompels
Ursula A
UA
D000256:Adenoviridae / Q000235:genetics; D000595:Amino Acid Sequence; D002459:Cell Fusion; D002460:Cell Line; D022801:Complementarity Determining Regions; D003587:Cytomegalovirus / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D005814:Genes, Viral; D014644:Genetic Variation; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D011995:Recombination, Genetic; D016415:Sequence Alignment; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*
D022801:Complementarity Determining Regions; D008562:Membrane Glycoproteins; D014759:Viral Envelope Proteins; C071440:glycoprotein H, Cytomegalovirus; C499358:glycoprotein H, Human cytomegalovirus; C439068:glycoprotein O, cytomegalovirus