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In Vitro and In Vivo Attenuation of Vesicular Stomatitis Virus (VSV) by Phosphoprotein Deletion
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Document Title
In Vitro and In Vivo Attenuation of Vesicular Stomatitis Virus (VSV) by Phosphoprotein Deletion
Author
Wongthida P, Jengarn J, Narkpuk J, Koonyosying P, Srisutthisamphan K, Wanitchang A, Leaungwutiwong P, Teeravechyan S, Jongkaewwattana A
Name from Authors Collection
Scopus Author ID
55279790400
Scopus Author ID
57003681700
Scopus Author ID
25824516500
Affiliations
National Science & Technology Development Agency - Thailand; National Center Genetic Engineering & Biotechnology (BIOTEC); National Science & Technology Development Agency - Thailand; National Center Genetic Engineering & Biotechnology (BIOTEC); Kasetsart University; Mahidol University
Type
Article
Source Title
PLOS ONE
ISSN
1932-6203
Year
2016
Volume
11
Issue
6
Page
-
Open Access
Green Published, gold, Green Submitted
Publisher
PUBLIC LIBRARY SCIENCE
DOI
10.1371/journal.pone.0157287
Format
Abstract
Vesicular stomatitis virus (VSV) is highly immunogenic and able to stimulate both innate and adaptive immune responses. However, its ability to induce adverse effects has held back the use of VSV as a potential vaccine vector. In this study we developed VSV-Delta P, a safe yet potent replication-defective recombinant VSV in which the phosphoprotein (P) gene was deleted. VSV-Delta P replicated only in supporting cells expressing P (BHK-P cells) and at levels more than 2 logs lower than VSV. In vivo studies indicated that the moderate replication of VSV-Delta P in vitro was associated with the attenuation of this virus in the mouse model, whereas mice intracranially injected with VSV succumbed to neurotoxicity. Furthermore, we constructed VSV and VSV-Delta P expressing a variety of antigens including hemagglutinin-neuraminidase (HN) from Newcastle disease virus (NDV), hemagglutinin (HA) from either a 2009 H1N1 pandemic influenza virus (pdm/09) or the avian H7N9. VSV and VSV-Delta P incorporated the foreign antigens on their surface resulting in induction of robust neutralizing antibody, serum IgG, and hemagglutination inhibition (HAI) titers against their corresponding viruses. These results indicated that VSV with P gene deletion was attenuated in vitro and in vivo, and possibly expressed the foreign antigen on its surface. Therefore, the P gene-deletion strategy may offer a potentially useful and safer approach for attenuating negative-sense RNA viruses which use phosphoprotein as a cofactor for viral replication.
Industrial Classification
Knowledge Taxonomy Level 1
Knowledge Taxonomy Level 2
Funding Sponsor
Cluster Program Management Office, National Science and Technology Development Agency, Thailand [P-14-51228]
License
CC BY
Rights
Authors
Publication Source
WOS