Multiple Functions for the Basic Amino Acids of the Human T-Cell Leukemia Virus Type 1 Matrix Protein in Viral Transmission
Multiple Functions for the Basic Amino Acids of the Human T-Cell Leukemia Virus Type 1 Matrix Protein in Viral Transmission
复制标题
人类 T 细胞白血病病毒 1 型基质蛋白的碱性氨基酸在病毒传播中的多种功能
作者：
I. Le Blanc;A. Rosenberg;M. Dokhelar
摘要我们利用碱性氨基酸的错义突变研究了人类T细胞白血病病毒1型(HTLV-1)Gag基质蛋白在病毒细胞间传播中的作用。在其他逆转录病毒中，这些碱性氨基酸聚集在蛋白质的N端，负责将Gag蛋白质靶向质膜。在HTLV-牛白血病病毒属的逆转录病毒中，碱性氨基酸分布在整个基质蛋白序列中。HTLV-1基质蛋白包含11个这样的残基。只有在基质蛋白的两个位置之一发生突变的突变病毒才能获得野生型表型。其他9种突变病毒的表型表明，碱性氨基酸参与了复制周期的不同步骤，包括一些在膜靶向之后的步骤。这9个突变中的大多数允许GAG前体的正常合成、运输和切割，但其中7个突变的颗粒释放受到很大影响。此外，四种突变蛋白具有正确的颗粒释放和包膜糖蛋白掺入，但不允许HTLV-1在细胞间传播。因此，尽管需要释放颗粒，但对于HTLV-1的细胞间传播来说，颗粒释放是不够的，基质蛋白的基本残基参与了病毒颗粒释放后发生的步骤。
ABSTRACT 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.
DOI：
10.1073/pnas.86.15.5781
发表时间：
1989-08-01
影响因子：
11.1
作者：
GOTTLINGER, HG;SODROSKI, JG;HASELTINE, WA
通讯作者：
HASELTINE, WA
DOI：
10.1073/pnas.87.2.523
发表时间：
1990-01-01
影响因子：
11.1
作者：
BRYANT, M;RATNER, L
通讯作者：
RATNER, L