Multiple functions for the basic amino acids of the human T-cell leukemia virus type 1 matrix protein in viral transmission

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 m issense mutations of the basic amino acids. These basic amino acids are clu stered at the N terminus of the protein in other retroviruses and are respo nsible for targeting the Gag proteins to the plasma membrane. In the HTLV-b ovine leukemia virus genus of retroviruses, the basic amino acids are distr ibuted throughout the matrix protein sequence. The HTLV-1 matrix protein co ntains 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 aci ds are involved at various steps of the replication cycle, including some a fter membrane targeting. Most of these nine mutations allowed normal synthe sis, transport, and cleavage of the Gag precursor, but particle release was greatly affected for seven of them. In addition, four mutated proteins wit h 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.