GENE SEQUENCE ANALYSIS OF TYPE D SRV 5 INFECTIOUS MOLECULAR CLONE: AIDS

D 型 SRV 5 感染性分子克隆的基因序列分析：艾滋病

• 批准号: 6247191
• 负责人: Michael K Axthelm
• 金额: $ 18.46万
• 依托单位: OREGON REGIONAL PRIMATE RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-05-01 至 1998-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6247191
• 关键词: AIDS; Mammalia; Primates; animal tissue; bacteria; biotechnology; communicable diseases; immunology; lymphatic system; virus

Type D simian retroviruses (SRV) are exogenous D type oncorna viruses that are the most significant cause of endemic acquired immunodeficiency syndrome (AIDS) in biomedical research colonies of macaques. Five serogroups of SRVs have been identified; however, only members of serogroups 1, 2 and 3 have been cloned and sequenced. Only members of serogroup 2 have been identified in wild macaque populations and the natural host of the other serogroups is not known. Serogroup 3 viruses have been recovered from humans but have been considered contaminants. Serogroup 5 contains a single prototype virus, D5/RHE/OR, isolated from a rhesus macaque imported to the ORPRC from the Peoples' Republic of China. This isolate produces severe immunodeficiency when transmitted to naive juvenile rhesus macaques. Serologic and hybridization studies suggest that SRV-5 is distinct from other serogroup members. We have sequenced the env and gag genes of a D5/RHE/OR infectious molecular clone. The D5/RHE/OR env polyprotein is 592 amino acid residues in length (gp70 and gp20 molecules are 400 and 192 amino acid residues, respectively), and contains 12 Asn-X-Ser(Thr) glycosylation sites, 11 of which are found within gp70. The D5/RHE/OR gp70 and gp20 molecules are 59.3 - 61.8% (range) and 83.9 - 84.4% (range) similar, respectively, to corresponding env glycoproteins identified for serogroups 1, 2 and 3. Interestingly, the D5/RHE/OR gp70 molecule is the largest among previously identified SRV serogroups (400 amino acid residues versus 388, 394 and 395 amino acid residues for D2/CEL/OR, Mason-Pfizer Monkey Virus (MPMV), and D1/RHE/CA, respectively). In the D5/RHE/OR gag polyprotein, proteins p10 and p27 (100 and 226 amino acid residues, respectively) are identical in length to those identified for serogroups 1, 2 and 3, while the lengths of p14, p4, p12 and p24 (94, 36, 82 and 63 amino acids, respectively) differ from those found in the other serogroups by one amino acid. The D5/RHE/OR gag region that is least conserved is p24; this region is 57.1%, 49.2% and 57.1% similar (at the amino acid level) to corresponding proteins found in D1/RHE/CA, D2/CEL/OR and MPMV, respectively. The D5/RHE/OR gag region that appears most conserved is p27, with 97.3%, 95.1% and 96.5% amino acid similarity for serogroups 1, 2 and 3, respectively. Sequencing the complete D5/RHE/OR genome will provide further insight into the genetic diversity of type D SRVs and may provide the beginning framework for understanding the molecular basis for serogroup differences in simian acquired immunodeficiency and phylogenetic studies.

D型猿猴逆转录病毒（D type simian retroviruses，SRV）是一种外源性D型肿瘤病毒， 病毒是地方性获得性感染的最重要原因， 免疫缺陷综合征（艾滋病）的生物医学研究殖民地， 猕猴 已经确定了5个血清型的SRVs;然而， 血清组1、2和3的成员已被克隆和测序。 只 血清群2的成员已经在野生猕猴中被鉴定 其他血清群的种群和自然宿主尚不清楚。 血清组3病毒已从人类中回收，但已被 被认为是污染物。 血清群5含有单一原型 病毒，D5/RHE/OR，从输入ORPRC的恒河猴分离 来自中华人民共和国。 该分离株产生严重的 免疫缺陷传播给天真的幼年恒河猴。 血清学和杂交研究表明，SRV-5是不同的， 其他血清群成员的感染 我们对env和gag基因进行了测序 D5/RHE/OR感染性分子克隆。 D5/RHE/OR环境 多聚蛋白的长度为592个氨基酸残基（gp 70和gp 20 分子分别为400和192个氨基酸残基），和 含有12个Asn-X-Ser（Thr）糖基化位点，其中11个被发现 在GP 70中。 D5/RHE/OR gp 70和gp 20分子为59.3 - 61.8%， （范围）和83.9 - 84.4%（范围）分别与 血清组1、2和3鉴定的相应env糖蛋白。 有趣的是，D5/RHE/OR gp 70分子是其中最大的分子。 先前鉴定的SRV血清群（400个氨基酸残基， D2/CEL/OR的388、394和395个氨基酸残基，Mason-Pfizer 猴病毒（MPMV）和D1/RHE/CA）。 在D5/RHE/OR gag多蛋白，蛋白质p10和p27（100和226个氨基酸 残基）在长度上与鉴定的那些相同 p14、p4、p12和p24的长度与血清群1、2和3的长度相比， (94，36，82和63个氨基酸）与发现的那些不同 在其他血清群中的氨基酸。 D5/RHE/OR gag区 保守性最低的是p24，分别为57.1%、49.2%和57.1%。 类似（在氨基酸水平上）的相应蛋白质中发现， D1/RHE/CA、D2/CEL/OR和MPMV。 D5/RHE/OR gag区 其中p27基因最为保守，分别有97.3%、95.1%和96.5%的氨基酸残基， 血清群1、2和3的酸相似性。 测序 完整的D5/RHE/OR基因组将进一步深入了解 D型SRVs的遗传多样性，并可能提供开始 了解血清群的分子基础的框架 猴获得性免疫缺陷和系统发育的差异 问题研究