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CEM T细胞系和WIL-2 B细胞系衍生物对人类免疫缺陷病毒反应的表型变异

Phenotypic variation in the response to the human immunodeficiency virus among derivatives of the CEM T and WIL-2 B cell lines.

作者信息

Chaffee S, Leeds J M, Matthews T J, Weinhold K J, Skinner M, Bolognesi D P, Hershfield M S

机构信息

Department of Pediatrics, Duke University Medical Center, Durham, North Carolina 27710.

出版信息

J Exp Med. 1988 Aug 1;168(2):605-21. doi: 10.1084/jem.168.2.605.

Abstract

Derivatives of the CEM T and WIL-2 B cell lines showed striking diversity in their responses to the HTLV-IIIB strain of the human immunodeficiency virus (HIV). Several stable phenotypic patterns could be defined, based on whether cells were permissive (P+, P-) for virus production, were sensitive or insensitive to cytopathic effects after infection by free virus (C+, C-), and whether they underwent fusion on contact with virus-infected cells (F+, F-). Although expression of CD4 was essential for infection by HTLV-IIIB, very low levels were sufficient for productive infection of WIL-2 derivatives. Conversely, some CEM T cell lines that expressed ample CD4, and which were able to bind virus gp120 and undergo fusion, did not support productive infection by free virus. One nonpermissive, CD4+ derivative of CEM could bind gp120 but failed to undergo fusion, suggesting an alteration in some membrane protein other than CD4 that is essential for virus entry and HIV-induced cell fusion. The AA2 derivative of the WIL-2 cell line is also described, which is remarkably permissive for HIV replication and exquisitely sensitive to virus cytopathic effect. The panel of related cell lines with different host-virus phenotypes could be useful for more precisely defining steps in the infectious cycle of HIV, and for identifying host cell genes and gene products that determine the outcome of HIV infection.

摘要

CEM T细胞系和WIL-2 B细胞系的衍生物在对人类免疫缺陷病毒(HIV)HTLV-IIIB株的反应中表现出显著的多样性。根据细胞对病毒产生是否允许(P+,P-)、对游离病毒感染后的细胞病变效应是否敏感或不敏感(C+,C-)以及它们与病毒感染细胞接触时是否发生融合(F+,F-),可以定义几种稳定的表型模式。虽然CD4的表达对于HTLV-IIIB感染至关重要,但极低水平的CD4就足以使WIL-2衍生物进行有效感染。相反,一些表达大量CD4且能够结合病毒gp120并发生融合的CEM T细胞系,却不支持游离病毒的有效感染。CEM的一种不允许感染、CD4+衍生物能够结合gp120,但未能发生融合,这表明除CD4外的某些膜蛋白发生了改变,而这些膜蛋白对于病毒进入和HIV诱导的细胞融合至关重要。还描述了WIL-2细胞系的AA2衍生物,它对HIV复制具有显著的允许性,并且对病毒细胞病变效应极为敏感。具有不同宿主-病毒表型的相关细胞系组合可能有助于更精确地定义HIV感染周期中的步骤,并有助于鉴定决定HIV感染结果的宿主细胞基因和基因产物。

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