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PMID: 9882334 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The YXXL sequences of a transmembrane protein of bovine leukemia virus are required for viral entry and incorporation of viral envelope protein into virions.

Journal of virology ·Vol. 73 ·No. 2 ·1999-02-00 ·Pages 1293-301

Inabe K, Nishizawa M, Tajima S, Ikuta K, Aida Y

Abstract

The cytoplasmic domain of an envelope transmembrane glycoprotein (gp30) of bovine leukemia virus (BLV) has two overlapping copies of the (YXXL)2 motif. The N-terminal motif has been implicated in in vitro signal transduction pathways from the external to the intracellular compartment and is also involved in infection and maintenance of high viral loads in sheep that have been experimentally infected with BLV. To determine the role of YXXL sequences in the replication of BLV in vitro, we changed the tyrosine or leucine residues of the N-terminal motif in an infectious molecular clone of BLV, pBLV-IF, to alanine to produce mutated proviruses designated Y487A, L490A, Y498A, L501A, and Y487/498A. Transient transfection of African green monkey kidney COS-1 cells with proviral DNAs that encoded wild-type and mutant sequences revealed that all of the mutated proviral DNAs synthesized mature envelope proteins and released virus particles into the growth medium. However, serial passages of fetal lamb kidney (FLK) cells, which are sensitive to infection with BLV, after transient transfection revealed that mutation of a second tyrosine residue in the N-terminal motif completely prevented the propagation of the virus. Similarly, Y498A and Y487/498A mutant BLV that was produced by the stably transfected COS-1 cells exhibited significantly reduced levels of cell-free virion-mediated transmission. Analysis of the protein compositions of mutant viruses demonstrated that lower levels of envelope protein were incorporated by two of the mutant virions than by wild-type and other mutant virions. Furthermore, a mutation of a second tyrosine residue decreased the specific binding of BLV particles to FLK cells and the capacity for viral penetration. Our data indicate that the YXXL sequences play critical roles in both viral entry and the incorporation of viral envelope protein into the virion during the life cycle of BLV.

MeSH Terms
Amino Acid Sequence Animals COS Cells Cattle Cell Line Cell-Free System DNA, Viral Leukemia Virus, Bovine/genetics,physiology Molecular Sequence Data Mutagenesis Proviruses/genetics Retroviridae Proteins, Oncogenic/chemistry,genetics,physiology Structure-Activity Relationship Transfection Viral Envelope Proteins/chemistry,genetics,physiology Virion/physiology Virus Assembly/physiology
Chemicals
DNA, Viral Retroviridae Proteins, Oncogenic Viral Envelope Proteins gp30 envelope transmembrane protein, Bovine leukemia virus
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Inabe K
Tsukuba Life Science Center, The Institute of Physical and Chemical Research (RIKEN), Tsukuba, Ibaraki 305-0074, Japan.
Nishizawa M
Tajima S
Ikuta K
Aida Y
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.73.2.1293-1301.1999
Published
1999-02-00
Pages
1293-301
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC103953
Subset
IM
External Links
PubMed source DOI: 10.1128/JVI.73.2.1293-1301.1999 PMC Full Text View journal details
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