Enhancement of HIV-1-induced syncytium formation in T cells by the tyrosyl kinase p56(lck)

被引:9
作者
Briand, G
Barbeau, B
Corbeil, J
Tremblay, M
机构
[1] CHU QUEBEC, CTR RECH INFECTIOL, ST FOY, PQ G1V 4G2, CANADA
[2] UNIV LAVAL, FAC MED, DEPT MICROBIOL, ST FOY, PQ G1V 4G2, CANADA
[3] UNIV CALIF SAN DIEGO, DEPT PATHOL, LA JOLLA, CA 92093 USA
关键词
D O I
10.1006/viro.1997.8518
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
The CD4 glycoprotein is the primary cellular receptor for human immunodeficiency virus type 1 (HIV-1) and has also been reported to be physically associated with p56(lck), a tyrosyl protein kinase. p56(lck) is a member of the src family of nonreceptor protein-tyrosine kinases and is expressed predominantly in T lymphocytes. Our objective was to study the effect of p56(lck) on the biology of HIV-1. For this purpose, we have stably transfected two human p56(lck)-negative T cell lines (C8166-45 and MT-2) with plasmids encoding for this cellular protein. Following coculture with HIV-1-infected cells or infection with cell-free virus, p56(lck)-expressing cell lines showed a greater propensity for virus-mediated syncytium formation than parental p56(lck)-negative cells. The enhancement of HIV-1-induced syncytium formation was not associated with the kinase activity of p56(lck), as demonstrated by experiments using a kinase-deficient mutant. However, the physical interaction between CD4 and p56(lck) was shown to be necessary to obtain the enhancement of syncytium formation since a mutated version of p56(lck), which is deficient in its capacity to associate with CD4, did not lead to an increase in virus-mediated cell-to-cell fusion events. Finally, we determined that cells transfected with wild-type and kinase-negative mutant p56(lck) showed a reduced rate of CD4 endocytosis compared to parental p56(lck)-negative cells. Together, these results suggest that p56(lck) can be seen as an accessory molecule facilitating HIV-1-mediated syncytium formation in T cells by a mechanism involving the stabilization of the CD4 molecule at the cell surface. (C) 1997 Academic Press.
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页码:10 / 19
页数:10
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