Functional characterization of the N termini of murine leukemia virus envelope proteins

Authors
Citation
Cw. Lu et Mj. Roth, Functional characterization of the N termini of murine leukemia virus envelope proteins, J VIROLOGY, 75(9), 2001, pp. 4357-4366
Citations number
65
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Microbiology
Journal title
JOURNAL OF VIROLOGY
ISSN journal
0022-538X → ACNP
Volume
75
Issue
9
Year of publication
2001
Pages
4357 - 4366
Database
ISI
SICI code
0022-538X(200105)75:9<4357:FCOTNT>2.0.ZU;2-8
Abstract
The function of the N terminus of the murine leukemia virus (MuLV) surface (SU) protein was examined. A series of five chimeric envelope proteins (Env ) were generated in which the N terminus of amphotropic 4070A was replaced by equivalent sequences from ecotropic Moloney MuLV (M-MuLV). Viral titers of these chimeras indicate that exchange with homologous sequences could be tolerated, up to V17eco/T15ampho (crossover III). Constructs encoding the first 28 amino acids (aa) of ecotropic M-MuLV resulted in Env expression an d binding to the receptor; however, the virus titer was reduced 5- to 45-fo ld, indicating a postbinding block. Additional exchange beyond the first 28 aa of ecotropic MuLV Env resulted in defective protein expression. These N -terminal chimeras were also introduced into the AE4 chimeric Env backbone containing the amphotropic receptor binding domain joined at the hinge regi on to the ecotropic SU C terminus. In this backbone, introduction of the fi rst 17 aa of the ecotropic Env protein significantly increased the titer co mpared to that of its parental chimera AE4, implying a functional coordinat ion between the N terminus of SU and the C terminus of the SU and/or transm embrane proteins. These data functionally dissect the N-terminal sequence o f the MuLV Env protein and identify differential effects on receptor-mediat ed entry.