Vaccinia virus induces cell fusion at acid pH and this activity is mediated by the N-terminus of the 14-kDa virus envelope protein.

TitleVaccinia virus induces cell fusion at acid pH and this activity is mediated by the N-terminus of the 14-kDa virus envelope protein.
Publication TypeJournal Article
Year of Publication1990
AuthorsGong SC, Lai CF, Esteban M
JournalVirology
Volume178
Issue1
Pagination81-91
Date Published1990 Sep
ISSN0042-6822
KeywordsAmino Acid Sequence, Animals, Base Sequence, Chromosome Mapping, DNA, Viral, Hydrogen-Ion Concentration, Membrane Fusion, Mice, Molecular Sequence Data, Mutation, Vaccinia, Vaccinia virus, Viral Envelope Proteins
Abstract

The mechanism by which the large-size poxviruses enter animal cells is not known. In this investigation we show that acid pH treatment of wild-type vaccinia virus-infected cells triggers strong fusion of cells in culture, with an optimum at pH 4.8. We have identified the virus-induced fusion protein as a 14-kDa envelope protein, based on the ability of a 14-kDa specific monoclonal antibody (mAbC3) to block vaccinia virus-induced fusion-from-within and fusion-from-without. We provide genetic evidence for a role of the 14-kDa protein in cell fusion, since insertion of the 14-kDa encoding gene into the genome of nonfusogenic mutant viruses generates heterozygous viruses that now acquire acid pH-dependent fusion activity. DNA sequence analyses of the 14-kDa encoding gene of the mutant viruses, 65-16 and 101-14, reveal N-terminal deletions of 46 and 10 amino acids, respectively. These deletions remove a small hydrophobic region at the N-terminus of the 14-kDa protein and prevent fusion. Our findings demonstrate that vaccinia virus can induce strong fusion of cells in culture at acid pH implying some entry of the virus by endocytosis, that the 14-kDa virus envelope protein is the fusogenic protein, and that the N-terminal proximal region is involved in fusion.

Alternate JournalVirology
PubMed ID2389560
Grant ListCA44262 / CA / NCI NIH HHS / United States