IDENTIFICATION OF A DETERMINANT WITHIN THE HUMAN IMMUNODEFICIENCY VIRUS-1 SURFACE ENVELOPE GLYCOPROTEIN CRITICAL FOR PRODUCTIVE INFECTION OF PRIMARY MONOCYTES
IDENTIFICATION OF A DETERMINANT WITHIN THE HUMAN IMMUNODEFICIENCY VIRUS-1 SURFACE ENVELOPE GLYCOPROTEIN CRITICAL FOR PRODUCTIVE INFECTION OF PRIMARY MONOCYTES
复制标题
DOI：
10.1073/pnas.88.8.3097
复制
发表时间：
1991-04-01
影响因子：
11.1
通讯作者：
RATNER, L
中科院分区：
文献类型：
--
作者：
WESTERVELT, P;GENDELMAN, HE;RATNER, L
在原代人单核细胞中，不同的人免疫缺陷病毒1型分离株的复制能力存在显著差异。为了研究这些差异的分子基础，通过来自亲单核细胞分离株（ADA）的分子克隆与在原代单核细胞培养物（HXB 2和NL 4 -3）中不能感染或复制的两个全长克隆的部分之间的相互DNA片段交换构建重组全长克隆。 来自含有编码vpu的ADA序列和表面包膜糖蛋白（gp 120）的N和C末端的前病毒克隆的病毒粒子不能在单核细胞中复制。 然而，283个碱基对的ADA序列编码的成熟gp 120蛋白的氨基酸240-333赋予高水平的病毒复制的能力，在初级单核细胞。 该ADA克隆的预测氨基酸序列与NL 4 -3和HXB 2在gp 120的该部分中的94个残基中的22个处不同，其包括整个第三可变结构域。 与CD 4结合有关的11个残基中只有2个位于gp 120的该区域，并且在HXB 2、NL 4 -3和ADA中相同。 ADA序列与三个额外的单核细胞复制型和三个单核细胞非复制型克隆的已发表氨基酸序列的比对表明，6个离散残基可能参与赋予初级单核细胞的生产性人类免疫缺陷病毒1型感染。
Profound differences exist in the replicative capacities of various human immunodeficiency virus 1 isolates in primary human monocytes. To investigate the molecular basis for these differences, recombinant full-length clones were constructed by reciprocal DNA fragment exchange between a molecular clone derived from a monocyte-tropic isolate (ADA) and portions of two full-length clones incapable of infection or replication in primary monocyte cultures (HXB2 and NL4-3). Virions derived from proviral clones that contained ADA sequences encoding vpu and the N and C termini of the surface envelope glycoprotein (gp120) were incapable of replication in monocytes. However, a 283-base-pair ADA sequence encoding amino acids 240-333 of the mature gp120 protein conferred the capacity for high-level virus replication in primary monocytes. The predicted amino acid sequence of this ADA clone differed from NL4-3 and HXB2 at 22 of 94 residues in this portion of gp120, which includes the entire third variable domain. Only 2 of 11 residues implicated in CD4 binding are located in this region of gp120 and are identical in HXB2, NL4-3, and ADA. Alignment of the ADA sequence with published amino acid sequences of three additional monocyte-replicative and three monocyte-nonreplicative clones indicates 6 discrete residues with potential involvement in conferring productive human immunodeficiency virus 1 infection of primary monocytes.