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世界卫生组织赞助的疫苗评估点的1型人类免疫缺陷病毒变异:选定病毒株的基因筛查、序列分析及初步生物学特性鉴定。世界卫生组织人类免疫缺陷病毒分离与特性鉴定网络。

HIV type 1 variation in World Health Organization-sponsored vaccine evaluation sites: genetic screening, sequence analysis, and preliminary biological characterization of selected viral strains. WHO Network for HIV Isolation and Characterization.

出版信息

AIDS Res Hum Retroviruses. 1994 Nov;10(11):1327-43. doi: 10.1089/aid.1994.10.1327.

DOI:10.1089/aid.1994.10.1327
PMID:7545977
Abstract

A laboratory network has been established by the World Health Organization (WHO) to systematically isolate and characterize HIV strains from different parts of the world, and to obtain information and reagents that would facilitate HIV vaccine development. Sixty-three HIV-1 isolates obtained from 224 specimens collected during 1992-1993 in Brazil, Rwanda, Thailand, and Uganda were characterized in this initial study. Virus strains were first genetically subtyped using three different screening methodologies: PCR-gag fingerprinting, RNase A mismatch, and heteroduplex mobility assay (HMA). In addition, selected viruses were sequenced in V3 (52 strains), C2-V3 (42 strains), gp120 (15 strains), and/or gp160 (8 strains) regions of their envelope genes. These studies identified viruses belonging to different sequence subtypes in the four countries: 16 subtype B and 1 subtype C strains in Brazil, 13 subtype A strains in Rwanda, 15 subtype E and 2 subtype B strains in Thailand, and 3 subtype A and 13 subtype D strains in Uganda. Comparison of sequence data with results from the genetic screening efforts identified the HMA as a rapid and reliable method for sequence subtype determinations. The majority of strains were collected from persons documented to have recently seroconverted to HIV-1 positivity, and most strains were found to have slow replication and low cytopathic characteristics and to be non-syncytium-inducing (slow/low-NSI phenotypes) in vitro, which, in many cases, correlated with the corresponding genotype and charge of the V3 loop amino acid sequences. This collection of HIV strains is presently being characterized immunologically and serologically, including neutralization assays, to define whether there are immunological correlates of the sequence subtypes. Identification of potential immunotypes would be of considerable importance for the further development of HIV vaccines.

摘要

世界卫生组织(WHO)建立了一个实验室网络,用于系统地分离和鉴定来自世界不同地区的HIV毒株,并获取有助于HIV疫苗研发的信息和试剂。在这项初步研究中,对1992年至1993年期间在巴西、卢旺达、泰国和乌干达收集的224份标本中获得的63株HIV-1分离株进行了鉴定。首先使用三种不同的筛选方法对病毒株进行基因亚型分型:PCR-gag指纹图谱法、核糖核酸酶A错配法和异源双链迁移率分析(HMA)。此外,对选定的病毒在其包膜基因的V3(52株)、C2-V3(42株)、gp120(15株)和/或gp160(8株)区域进行了测序。这些研究确定了四个国家中属于不同序列亚型的病毒:巴西有16株B亚型和1株C亚型毒株,卢旺达有13株A亚型毒株,泰国有15株E亚型和2株B亚型毒株,乌干达有3株A亚型和13株D亚型毒株。将序列数据与基因筛选结果进行比较,确定HMA是一种快速可靠的序列亚型测定方法。大多数毒株是从记录显示最近血清转化为HIV-1阳性的人身上收集的,并且发现大多数毒株在体外具有复制缓慢、细胞病变特征低和非合胞体诱导(慢/低-NSI表型)的特点,在许多情况下,这与V3环氨基酸序列的相应基因型和电荷相关。目前正在对这批HIV毒株进行免疫学和血清学鉴定,包括中和试验,以确定序列亚型是否存在免疫相关性。鉴定潜在的免疫型对于HIV疫苗的进一步研发具有相当重要的意义。

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