SYNCYTIUM-INDUCING AND NON-SYNCYTIUM-INDUCING CAPACITY OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 SUBTYPES OTHER THAN B - PHENOTYPIC AND GENOTYPIC CHARACTERISTICS
SYNCYTIUM-INDUCING AND NON-SYNCYTIUM-INDUCING CAPACITY OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 SUBTYPES OTHER THAN B - PHENOTYPIC AND GENOTYPIC CHARACTERISTICS
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DOI：
10.1089/aid.1994.10.1387
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发表时间：
1994-11-01
影响因子：
1.5
通讯作者：
KORBER, B
中科院分区：
文献类型：
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作者：
DEWOLF, F;HOGERVORST, E;KORBER, B
HIV-1亚型B包膜的第三可变区（V3）环内位置11和25处的带正电荷的氨基酸取代已显示与病毒的合胞体诱导（SI）表型相关。本研究旨在检测HIV-1亚型（非B）中SI和NSI相关的V3突变。从来自巴西、卢旺达、泰国和乌干达的53名最近感染者的53份病毒储备和26份同源血浆样本中分离出HIV-1 RNA。将病毒包膜的C2-V3区转化为cDNA，扩增并测序。在53份原代病毒储备样品中，通过测量MT-2细胞中的合胞体诱导能力（以区分SI和NSI表型）对49份进行生物表型分析。此外，在原代分离物通过PHA刺激的供体PBMC传代后，在U937-2、CEM、MT-2和Jurkat-tat细胞系中测定复制能力（以区分快速/高和缓慢/低表型）。经序列分析，A亚型9株（17.0%），B亚型15株（28.3%），C亚型1株（1.9%），D亚型13株（24.5%），E亚型15株（28.3%）。从26个同源血浆样品中获得的病毒RNA的序列分析证实了与原代病毒分离株相比血浆中序列群体的同质性。在检测的49种病毒中，12种具有SI表型，5种被确认为快速/高复制，4种似乎是慢/低模式3复制。在49例中，29例具有NSI表型，24例被证实为慢/低模式1或2，3例似乎为慢/低模式3复制。V3环氨基酸位置11和25处的突变分析显示，10/12（83.3%）的SI病毒具有SI相关的V3突变，并且28/29（96.6%）的NSI病毒缺乏这些突变。V3环异质性，长度多态性，和大量的带正电荷的氨基酸取代是最常见的亚型D变异。这些结果表明，SI和NSI病毒之间的表型差异以及生物学表型与V3突变的相关性均存在于除B以外的HIV-1亚型中。
Positively charged amino acid substitutions at positions 11 and 25 within the loop of the third variable region (V3) of HIV-1 subtype B envelope have been shown to be associated with the syncytium-inducing (SI) phenotype of the virus. The present study was designed to examine SI and NSI-associated V3 mutations in HIV-1 subtypes other than B. HIV-1 RNA was isolated from 53 virus stocks and 26 homologous plasma samples from 53 recently infected individuals from Brazil, Rwanda, Thailand, and Uganda. The C2-V3 region of the viral envelope was converted to cDNA, amplified, and sequenced. Of 53 primary virus stock samples 49 were biologically phenotyped through measurement of the syncytium-inducing capacity in MT-2 cells (to differentiate between SI and NSI phenotypes). In addition, after passage of primary isolates through PHA stimulated donor PBMC, the replication capacity was determined in U937-2, CEM, MT-2, and Jurkat-tat cell lines (to differentiate rapid/high and slow/low phenotypes). According to the sequence analysis 9 (17.0%) of the viruses belonged to subtype A, 15 (28.3%) to subtype B, 1 (1.9%) to subtype C, 13 (24.5%) to subtype D, and 15 (28.3%) to subtype E. Sequence analysis of virus RNA, obtained from 26 homologous plasma samples, confirmed the homogeneity of sequence populations in plasma compared to primary virus isolates. Of the 49 viruses tested 12 had the SI phenotype, 5 were confirmed to be rapid/high, and 4 appeared to be slow/low pattern 3 replicating. Of 49, 29 had the NSI phenotype, 24 were confirmed to be slow/low pattern 1 or 2, and 3 appeared to be slow/low pattern 3 replicating. Analysis of mutations at V3 loop amino acid positions 11 and 25 revealed that 10/12 (83.3%) of the SI viruses had SI-associated V3 mutations and that 28/29 (96.6%) of the NSI viruses lacked these mutations. V3 loop heterogeneity, length polymorphism, and a high number of positively charged amino acid substitutions were most frequently found among subtype D variants. These results indicate that both the phenotypic distinction between SI and NSI viruses and the association of biological phenotype with V3 mutations is present among HIV-1 subtypes other than B.