In:
PLOS ONE, Public Library of Science (PLoS), Vol. 17, No. 2 ( 2022-2-9), p. e0263707-
Abstract:
Newcastle Disease Virus (NDV) is an avian RNA virus, which was shown to be effective and safe for use in oncolytic viral therapy for several tumour malignancies. The presence of a multi basic cleavage site (MBCS) in the fusion protein improved its oncolytic efficacy in vitro and in vivo . However, NDV with a MBCS can be virulent in poultry. We aimed to develop an NDV with a MBCS but with reduced virulence for poultry while remaining effective in killing human tumour cells. To this end, the open reading frame of the V protein, an avian specific type I interferon antagonist, was disrupted by introducing multiple mutations. NDV with a mutated V gene was attenuated in avian cells and chicken and duck eggs. Although this virus still killed tumour cells, the efficacy was reduced compared to the virulent NDV. Introduction of various mutations in the fusion (F) and hemagglutinin-neuraminidase (HN) genes slightly improved this efficacy. Taken together, these data demonstrated that NDV with a MBCS but with abrogation of the V protein ORF and mutations in the F and HN genes can be safe for evaluation in oncolytic viral therapy.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0263707
DOI:
10.1371/journal.pone.0263707.g001
DOI:
10.1371/journal.pone.0263707.g002
DOI:
10.1371/journal.pone.0263707.g003
DOI:
10.1371/journal.pone.0263707.g004
DOI:
10.1371/journal.pone.0263707.g005
DOI:
10.1371/journal.pone.0263707.t001
DOI:
10.1371/journal.pone.0263707.t002
DOI:
10.1371/journal.pone.0263707.t003
DOI:
10.1371/journal.pone.0263707.s001
DOI:
10.1371/journal.pone.0263707.s002
DOI:
10.1371/journal.pone.0263707.s003
DOI:
10.1371/journal.pone.0263707.r001
DOI:
10.1371/journal.pone.0263707.r002
DOI:
10.1371/journal.pone.0263707.r003
DOI:
10.1371/journal.pone.0263707.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2267670-3
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