Lobato Robert L, Kim Eun-Young, Kagan Ronald M, Merigan Thomas C
Center for AIDS Research, Stanford University School of Medicine, 300 Pasteur Drive, Grant Building S-156, Stanford, CA 94305-5107, USA.
AIDS Res Hum Retroviruses. 2002 Jul 1;18(10):733-6. doi: 10.1089/088922202760072375.
An HIV-1 isolate possessing a 15-base insertion between codons 69 and 70 of the reverse transcriptase (RT) gene was derived from a patient plasma sample. Investigation of the insertion sequence revealed that this mutation is an ectopic duplication of the first 15 bases of the HIV-1 envelope gene. Phenotypic analysis yielded the following increases in resistance: 371-fold to zidovudine, 84-fold to lamivudine, 32-fold to abacavir, 15-fold to stavudine, 12-fold to didanosine, and 4-fold to zalcitabine. Phenotypic studies suggested that this change does not detract from the overall fitness of the virus. Together, data from this investigation support two conclusions. First, a previously unreported mechanism exists for generating diversity in HIV-1, namely long-distance duplication of genetic material from one portion of the genome to another. Second, large insertions in this region of RT are well tolerated and can confer high levels of resistance to multiple nucleoside analogue reverse transcriptase inhibitors.
一株在逆转录酶（RT）基因第69和70密码子之间存在15个碱基插入的HIV-1分离株源自一份患者血浆样本。对插入序列的研究表明，该突变是HIV-1包膜基因前15个碱基的异位重复。表型分析显示耐药性有以下增加：对齐多夫定增加371倍，对拉米夫定增加84倍，对阿巴卡韦增加32倍，对司他夫定增加15倍，对去羟肌苷增加12倍，对扎西他滨增加4倍。表型研究表明，这种变化不会损害病毒的整体适应性。综合来看，该研究数据支持两个结论。第一，存在一种以前未报道的在HIV-1中产生多样性的机制，即遗传物质从基因组的一部分远距离重复到另一部分。第二，RT这一区域的大插入具有良好的耐受性，并且可以赋予对多种核苷类似物逆转录酶抑制剂的高水平耐药性。
