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含有 SHIV89.6P 包膜基因的 SIVagm 复制能力差,且无致病性。

SIVagm containing the SHIV89.6P Envelope gene replicates poorly and is non-pathogenic.

机构信息

Division of Medical Biotechnology, Paul-Ehrlich-Institut, Langen, Germany.

Robert-Koch-Institut, Berlin, Germany.

出版信息

Virology. 2010 Mar 30;399(1):87-97. doi: 10.1016/j.virol.2009.12.032. Epub 2010 Jan 25.

Abstract

SIVagm does not induce disease in its African green monkey (AGM) host. In comparison, the hybrid simian-human immunodeficiency virus SHIV89.6P that carries the HIV env gene induces disease in rhesus macaques more rapidly than the SIVmac parent virus. To address the possibility that this enhancement of disease by HIV env would also occur when present in SIVagm, a full-length SIVagm/89.6Penv chimeric lentivirus genome (termed SHIV-MP) was constructed. SHIV-MP replicated similarly to SIVagm in simian peripheral blood mononuclear cells (PBMCs). In inoculated AGMs, rhesus macaques and pig-tailed (PT) macaques the absolute number of CD4(+) T lymphocytes remained at normal levels. The peak levels of productively infected cells in SHIV-MP-infected monkeys ranged from 10(1) to 10(2) per 10(6) PBMCs, while in SIVagm infected macaques the levels were 10-100-fold higher. The env gene of SHIV89.6P therefore appears insufficient to confer acute pathogenicity to a non-pathogenic primate lentivirus due to poor in vivo replication.

摘要

SIVagm 在其非洲绿猴(AGM)宿主中不会引起疾病。相比之下,携带 HIV env 基因的杂交猴免疫缺陷病毒 SHIV89.6P 在恒河猴中引起疾病的速度比 SIVmac 亲本病毒更快。为了研究 HIV env 的这种增强疾病的可能性是否也会出现在 SIVagm 中,构建了全长 SIVagm/89.6Penv 嵌合慢病毒基因组(称为 SHIV-MP)。SHIV-MP 在猿外周血单核细胞(PBMCs)中的复制与 SIVagm 相似。在接种的 AGM、恒河猴和猪尾猴(PT)中,CD4+T 淋巴细胞的绝对数量保持在正常水平。在 SHIV-MP 感染的猴子中,产感染细胞的峰值水平为每 106 PBMCs 中有 101 到 102 个,而在 SIVagm 感染的猴子中,水平高 10-100 倍。由于体内复制不良,SHIV89.6P 的 env 基因似乎不足以赋予非致病性灵长类慢病毒急性致病性。

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