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Journal of Virology, March 1999, p. 1860-1867, Vol. 73, No. 3
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Multiple Functions for the Basic Amino Acids of the
Human T-Cell Leukemia Virus Type 1 Matrix Protein in Viral
Transmission
Isabelle
Le Blanc,
Arielle R.
Rosenberg, and
Marie-Christine
Dokhélar*
INSERM U332, Institut Cochin de
Génétique Moléculaire, Paris, France
Received 23 June 1998/Accepted 7 December 1998
We studied the involvement of the human T-cell leukemia virus type
1 (HTLV-1) Gag matrix protein in the cell-to-cell transmission of the
virus using missense mutations of the basic amino acids. These basic
amino acids are clustered at the N terminus of the protein in other
retroviruses and are responsible for targeting the Gag proteins to the
plasma membrane. In the HTLV-bovine leukemia virus genus of
retroviruses, the basic amino acids are distributed throughout the
matrix protein sequence. The HTLV-1 matrix protein contains 11 such
residues. A wild-type phenotype was obtained only for mutant viruses
with mutations at one of two positions in the matrix protein. The
phenotypes of the other nine mutant viruses showed that the basic amino
acids are involved at various steps of the replication cycle, including
some after membrane targeting. Most of these nine mutations allowed
normal synthesis, transport, and cleavage of the Gag precursor, but
particle release was greatly affected for seven of them. In addition,
four mutated proteins with correct particle release and envelope
glycoprotein incorporation did not however permit cell-to-cell
transmission of HTLV-1. Thus, particle release, although required, is
not sufficient for the cell-to-cell transmission of HTLV-1, and the
basic residues of the matrix protein are involved in steps that occur
after viral particle release.
*
Corresponding author. Mailing address: INSERM U332,
Institut Cochin de Génétique Moléculaire, 22, rue
Méchain, 75014 Paris, France. Phone: 33 1 40 51 64 81. Fax: 33 1 40 51 77 49. E-mail: dokhelar{at}cochin.inserm.fr.
Journal of Virology, March 1999, p. 1860-1867, Vol. 73, No. 3
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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