A second-site suppressor significantly improves the defective phenotype imposed by mutation of an aromatic residue in the N-terminal domain of the HIV-1 capsid protein.
A second-site suppressor significantly improves the defective phenotype imposed by mutation of an aromatic residue in the N-terminal domain of the HIV-1 capsid protein.
复制标题
第二位点抑制子显着改善了 HIV-1 衣壳蛋白 N 末端结构域中芳香族残基突变造成的缺陷表型。
DOI：
10.1016/j.virol.2006.09.027
复制
发表时间：
2007
期刊：
影响因子：
3.7
通讯作者：
Levin,JudithG
中科院分区：
文献类型：
--
作者：
Tang,Shixing;Ablan,Sherimay;Dueck,Megan;Ayala-López,Wilfredo;Soto,Brenda;Caplan,Margaret;Nagashima,Kunio;Hewlett,IndiraK;Freed,EricO;Levin,JudithG
The HIV-1 capsid (CA) protein plays an important role in virus assembly and infectivity. Previously, we showed that Ala substitutions in the N-terminal residues Trp23 and Phe40 cause a severely defective phenotype. In searching for mutations at these positions that result in a non-lethal phenotype, we identified one candidate, W23F. Mutant virions contained aberrant cores, but unlike W23A, also displayed some infectivity in a single-round replication assay and delayed replication kinetics in MT-4 cells. Following long-term passage in MT-4 cells, two second-site mutations were isolated. In particular, the W23F/V26I mutation partially restored the wild-type phenotype, including production of particles with conical cores and wild-type replication kinetics in MT-4 cells. A structural model is proposed to explain the suppressor phenotype. These findings describe a novel occurrence, namely suppression of a mutation in a hydrophobic residue that is critical for maintaining the structural integrity of CA and proper core assembly.
