Mechanisms of loss of foreign gene expression in recombinant vesicular stomatitis viruses.
Publication/Presentation Date
9-1-2001
Abstract
We investigated the stability and mechanisms of loss of foreign gene expression in two recombinant vesicular stomatitis viruses (VSVs). A recombinant expressing the cellular CD4 protein exhibited remarkable stability of foreign gene expression. However, after 26 sequential passages, a mutant no longer expressing CD4 was recovered from the virus stock. Sequencing of the CD4 coding region in this mutant revealed a single nucleotide deletion causing a frameshift and termination of protein synthesis. A second VSV recombinant expressing the measles virus F protein grew poorly and exhibited extreme instability of expression of the F protein. Expression of F protein was lost rapidly through mutations of the upstream transcription termination site from (3')AUAC(5') to (3')AUAU(5'), as well as lengthening of the subsequent U(7) tract that is the template for poly(A) addition to VSV G mRNA. Such mutations resulted in fusion of the F mRNA to the 3' end of the G mRNA, making the F protein translation initiation codon inaccessible. We suggest that the VSV polymerase is error prone during replication of the U(7) tract, providing a rapid means for complete elimination of expression of proteins that are toxic to the virus life cycle.
Volume
287
Issue
2
First Page
427
Last Page
435
ISSN
0042-6822
Published In/Presented At
Quiñones-Kochs, M. I., Schnell, M. J., Buonocore, L., & Rose, J. K. (2001). Mechanisms of loss of foreign gene expression in recombinant vesicular stomatitis viruses. Virology, 287(2), 427–435. https://doi.org/10.1006/viro.2001.1058
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
11531419
Department(s)
Administration and Leadership
Document Type
Article