The dengue virus type 2 envelope protein fusion peptide is essential for membrane fusion

Journal Article · Wed Jan 20 00:00:00 EST 2010 · Virology

DOI:https://doi.org/10.1016/j.virol.2009.10.027· OSTI ID:21357587

Butrapet, Siritorn; Moss, Kelly J; Childers, Thomas ^[1]; Erb, Steven M ^[2]; Calvert, Amanda E; Silengo, Shawn J; Kinney, Richard M ^[1]; Blair, Carol D ^[2]; Roehrig, John T ^[1]

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1. Division of Vector-Borne Infectious Diseases, Centers for Disease Control and Prevention, Public Health Service, U.S. Department of Health and Human Services, 3150 Rampart Rd., Fort Collins, CO 80521 (United States)
2. Arthropod-borne and Infectious Diseases Laboratory, Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80523 (United States)

The flaviviral envelope (E) protein directs virus-mediated membrane fusion. To investigate membrane fusion as a requirement for virus growth, we introduced 27 unique mutations into the fusion peptide of an infectious cDNA clone of dengue 2 virus and recovered seven stable mutant viruses. The fusion efficiency of the mutants was impaired, demonstrating for the first time the requirement for specific FP AAs in optimal fusion. Mutant viruses exhibited different growth kinetics and/or genetic stabilities in different cell types and adult mosquitoes. Virus particles could be recovered following RNA transfection of cells with four lethal mutants; however, recovered viruses could not re-infect cells. These viruses could enter cells, but internalized virus appeared to be retained in endosomal compartments of infected cells, thus suggesting a fusion blockade. Mutations of the FP also resulted in reduced virus reactivity with flavivirus group-reactive antibodies, confirming earlier reports using virus-like particles.

• OSTI ID: 21357587
• Journal Information: Virology, Vol. 396, Issue 2; Other Information: DOI: 10.1016/j.virol.2009.10.027; PII: S0042-6822(09)00651-5; Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0042-6822
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
MEMBRANES
MUTAGENESIS
MUTANTS
MUTATIONS
PEPTIDES
REACTIVITY
RNA
VIRUSES
MICROORGANISMS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
PARASITES
PROTEINS