Matsuoka-Aizawa Saori, Gatanaga Hiroyuki, Sato Hironori, Koike Kazuhiko, Kimura Satoshi, Oka Shinichi
AIDS Clinical Center, International Medical Center of Japan, 1-21-1, Toyama, Shinjuku-ku, Tokyo 162-8655, Japan.
Antiviral Res. 2006 Jun;70(2):51-9. doi: 10.1016/j.antiviral.2006.01.004. Epub 2006 Feb 3.
We previously described a clinical human immunodeficiency virus type-1 (HIV-1) isolate, CL-4, which showed nelfinavir (NFV)-dependent enhancement of replication (Matsuoka-Aizawa, S., Sato, H., Hachiya, A., Tsuchiya, K., Takebe, Y., Gatanaga, H., Kimura, S., Oka, S, 2003. Isolation and molecular characterization of a nelfinavir (NFV)-resistant human immunodeficiency virus type 1 that exhibits NFV-dependent enhancement of replication. J. Virol. 77, 318-327.). To identify the responsible region(s) of HIV-1 proteins for such replication enhancement, we constructed a panel of recombinant HIV-1 clones harboring portions of the Gag and protease of CL-4 and analyzed their replication capabilities and Gag processing patterns. Our data suggested that the substitutions in the matrix and N-terminal half of capsid of CL-4 were indispensable for the NFV-dependent enhancement of replication and that NFV facilitated the cleavage between the matrix and capsid of the Gag precursor harboring these substitutions. The substitutions in C-terminal half of capsid rather decreased the cleavability of Gag precursor and NFV counteracted such negative impact. Efficient replication enhancement with NFV can be observed only in the presence of the substitutions in entire Gag and protease of CL-4.
我们之前描述了一种临床1型人类免疫缺陷病毒（HIV-1）分离株CL-4，其显示出对奈非那韦（NFV）依赖性的复制增强作用（松冈爱泽，S.，佐藤，H.，八谷，A.，土屋，K.，武部，Y.，加田名贺，H.，木村，S.，冈，S，2003年。一种对奈非那韦（NFV）耐药的1型人类免疫缺陷病毒的分离及分子特征，该病毒表现出对NFV依赖性的复制增强。《病毒学杂志》77，318 - 327页）。为了确定HIV-1蛋白中负责这种复制增强的区域，我们构建了一组携带CL-4的部分Gag和蛋白酶的重组HIV-1克隆，并分析了它们的复制能力和Gag加工模式。我们的数据表明，CL-4的基质和衣壳N端一半的替换对于NFV依赖性的复制增强是不可或缺的，并且NFV促进了携带这些替换的Gag前体在基质和衣壳之间的切割。衣壳C端一半的替换反而降低了Gag前体的可切割性，而NFV抵消了这种负面影响。只有在CL-4的整个Gag和蛋白酶中存在替换时，才能观察到NFV对复制的有效增强作用。
