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Biotechnol Bioeng ; 114(10): 2289-2297, 2017 10.
Article in English | MEDLINE | ID: mdl-28498621

ABSTRACT

Despite all the advantages that cell-cultured influenza vaccines have over egg-based influenza vaccines, the inferior productivity of cell-culture systems is a major drawback that must be addressed. BST-2 (tetherin) is a host restriction factor which inhibits budding-out of various enveloped viruses from infected host cells. We developed BST-2-deficient MDCK and Vero cell lines to increase influenza virus release in cell culture. BST-2 gene knock-out resulted in increased release of viral particles into the culture medium, by at least 2-fold and up to 50-fold compared to release from wild-type counterpart cells depending on cell line and virus type. The effect was not influenza virus/MDCK/Vero-specific, but was also present in a broad range of host cells and virus families; we observed similar results in murine, human, canine, and monkey cell lines with viruses including MHV-68 (Herpesviridae), influenza A virus (Orthomyxoviridae), porcine epidemic diarrhea virus (Coronaviridae), and vaccinia virus (Poxviridae). Our results suggest that the elimination of BST-2 expression in virus-producing cell lines can enhance the production of viral vaccines. Biotechnol. Bioeng.2017;114: 2289-2297. © 2017 Wiley Periodicals, Inc.


Subject(s)
Antigens, CD/genetics , Genetic Enhancement/methods , Influenza Vaccines/biosynthesis , Orthomyxoviridae/growth & development , Orthomyxoviridae/isolation & purification , Virion/isolation & purification , Virion/metabolism , Animals , Chlorocebus aethiops , Dogs , GPI-Linked Proteins/genetics , Gene Knockdown Techniques , Influenza Vaccines/isolation & purification , Madin Darby Canine Kidney Cells , Metabolic Engineering/methods , Orthomyxoviridae/genetics , Vero Cells , Virion/genetics
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