A highly pathogenic simian human immunodeficiency virus with genetic changes in cynomolgus monkey
A highly pathogenic simian human immunodeficiency virus with genetic changes in cynomolgus monkey
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DOI：
10.1099/0022-1317-80-5-1231
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发表时间：
1999-05-01
影响因子：
3.8
通讯作者：
Honda, M
中科院分区：
文献类型：
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作者：
Shinohara, K;Sakai, K;Honda, M
通过食蟹猴p-SHIV的血清传代获得一株高致病性猴/人免疫缺陷病毒（SHIV），命名为C2/1，该SHIV毒株含有致病性人免疫缺陷病毒1 86,6的env基因，在SHIV-C2/1感染后1周内，所有实验动物外周血和各淋巴器官中CD4（+）淋巴细胞减少，出现腹泻症状，体重未增加，随后出现强烈的病毒血症。在感染shiv - c2 /1病毒后4周检测到血清中Env蛋白抗体，而在感染shiv - c2 /1病毒的动物中没有抗gag抗体反应。相比之下，在感染p-SHIV或非致病性SHIV-MN的动物中均存在抗gag和抗env抗体反应。SHIV-C菌株分离株的env基因测序显示，env C2和V3区域的氨基酸变化保守，包括带负电荷的氨基酸变化，gp41细胞质区域的氨基酸变化包括42个氨基酸缺失，以及Nef蛋白。SHIV- c2 /1-猴致病性模型表明，SHIV感染的病毒特异性致病性可能与动物体内缺乏抗gag抗体反应有关，可能是由体内血清传代过程中的遗传变化引起的。
A highly pathogenic simian/human immunodeficiency virus (SHIV), designated C2/1, was obtained by serum passages in cynomolgus monkeys of p-SHIV, an SHIV strain that contains the env gene of pathogenic human immunodeficiency virus type 1 89,6, CD4(+) lymphocyte depletion was induced within 1 week of the SHIV-C2/1 infection in peripheral blood as well as in various lymphoid organs in all the animals tested, with symptoms of diarrhoea and no increase in body weight, followed by intense viraemia, Serum antibody against Env protein was detected from 4 weeks after the virus infection, while the anti-Gag antibody response was absent in the SHIV-C2/1-infected animals. In contrast, both anti-Gag and anti-Env antibody responses were present in animals infected with p-SHIV or the non-pathogenic SHIV-MN. Sequencing of the env gene of isolates of SHIV-C strains showed conserved amino acid changes in the Env C2 and V3 regions that included changes to negatively charged amino acids, in the cytoplasmic region of gp41 that included a 42 amino acid deletion, and in the Nef protein. The pathogenic SHIV-C2/1-monkey model suggests that virus-specific pathogenicity in SHIV infection may be associated with the absence of anti-Gag antibody responses in animals and may be caused by genetic changes during serum passage in vivo.