The m74 gene product of murine cytomegalovirus (MCMV) is a functional homolog of human CMV gO and determines the entry pathway of MCMV.
The glycoprotein gO (UL74) of human cytomegalovirus (HCMV) forms a complex with gH/gL. Virus mutants with a deletion of gO show a defect in secondary envelopment with the consequence that virus spread is restricted to a cell-associated pathway. Here we report that the positional homolog of HCMV gO, m74 of mouse CMV (MCMV), codes for a glycosylated protein which also forms a complex with gH (M75). m74 knockout mutants of MCMV show the same spread phenotype as gO knockout mutants of HCMV, namely, a shift from supernatant-driven to cell-associated spread. We could show that this phenotype is due to a reduction of infectious virus particles in cell culture supernatants. m74 knockout mutants enter fibroblasts via an energy-dependent and pH-sensitive pathway, whereas in the presence of an intact m74 gene product, entry is neither energy dependent nor pH sensitive. This entry phenotype is shared by HCMV expressing or lacking gO. Our data indicate that the m74 and UL74 gene products both codetermine CMV spread and CMV entry into cells. We postulate that MCMV, like HCMV, expresses alternative gH/gL complexes which govern cell-to-cell spread of the virus.
Scrivano
Laura
L
Max von Pettenkofer-Institut, Lehrstuhl Virologie, Feodor-Lynen Strasse 25, D-81377 Munich, Germany. .
Esterlechner
Jasmina
J
Mühlbach
Hermine
H
Ettischer
Nicole
N
Hagen
Christoph
C
Grünewald
Kay
K
Mohr
Christian A
CA
Ruzsics
Zsolt
Z
Koszinowski
Ulrich
U
Adler
Barbara
B
D000818:Animals; D002478:Cells, Cultured; D003470:Culture Media; D003587:Cytomegalovirus / Q000235:genetics / Q000502:physiology; D005347:Fibroblasts / Q000821:virology; D055786:Gene Knockout Techniques; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018146:Muromegalovirus / Q000235:genetics / Q000502:physiology*; D011485:Protein Binding; D055503:Protein Multimerization; D014759:Viral Envelope Proteins / Q000235:genetics / Q000502:physiology*; D019562:Viral Load; D010948:Viral Plaque Assay; D053586:Virus Internalization
D003470:Culture Media; D008562:Membrane Glycoproteins; D014759:Viral Envelope Proteins; C439068:glycoprotein O, cytomegalovirus