Reduced HIV-1 infectability of CD4+ lymphocytes from exposed-uninfected individuals:: Association with low expression of CCR5 and high production of β-chemokines
Reduced HIV-1 infectability of CD4+ lymphocytes from exposed-uninfected individuals:: Association with low expression of CCR5 and high production of β-chemokines
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DOI：
10.1006/viro.1998.9082
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发表时间：
1998-04-25
期刊：
影响因子：
3.7
通讯作者：
Koup, RA
中科院分区：
文献类型：
--
作者：
Paxton, WA;Liu, R;Koup, RA
我们检测了从CCR5野生型个体、CCR5 Delta32等位基因杂合子个体和具有CD_4(+)淋巴细胞对M嗜性病毒复制无效的HIV-L暴露但未感染的(EU)个体中分离的CD_4(+)淋巴细胞对人类免疫缺陷病毒1型的感染性。欧盟个体中没有发现Delta 32等位基因的杂合子。从CCR5/Delta 32和EU个体分离的CD4(+)淋巴细胞被M嗜性病毒分离株HIV-1感染的几率低于CCR5/CCR5对照个体，但与T嗜性病毒分离株的感染性相同。对M嗜性病毒分离株复制的限制与CCR5基因的任何深刻的基因变化无关。CCR5/Delta 32和CCR5/CCR5 EU患者的CD4(+)淋巴细胞对重组β-趋化因子RANTES、MIP-1α和MIP-1β的抑制作用比CCR5/CCR5对照组的CD4(+)淋巴细胞更敏感。欧盟人的CD4(+)淋巴细胞对重组β-趋化因子的敏感性增加，CCR5的表面表达较低。CCR5低表达和高分泌β-趋化因子的表型与细胞对M嗜性HIV-1的感染性降低有关。这种表型也可能与防止HIV-1的性传播有关。(C)1998年学术出版社。
We examined the human immunodeficiency virus type 1 infectability of CD4(+) lymphocytes isolated from CCR5 wild-type individuals, individuals heterozygous for the Delta 32 allele of CCR5, and HIV-l-exposed but uninfected (EU) individuals who had CD4(+) lymphocytes refractory to M-tropic viral replication. None of the EU individuals were found to be heterozygous for the Delta 32 allele. The CD4(+) lymphocytes isolated from CCR5/Delta 32 and EU individuals were less infectable with an M-tropic viral isolate of HIV-1 than CCR5/CCR5 control individuals but were equally as infectable with a T-tropic viral isolate. The restriction to M-tropic viral isolate replication did not associate with any profound genotypic change in the CCR5 gene. CD4(+) lymphocytes from CCR5/Delta 32 and CCR5/CCR5 EU individuals were more sensitive to the HIV-inhibitory effects of the recombinant beta-chemokines RANTES, MIP-1 alpha, and MIP-1 beta than were CD4(+) lymphocytes from CCR5/CCR5 control individuals. CD4(+) lymphocytes from EU individuals also showed increased sensitivity to recombinant beta-chemokines and low surface expression of CCR5. A phenotype of low CCR5 expression and high secretion of beta-chemokines is associated with reduced infectability of cells by M-tropic HIV-1. This phenotype may also be associated with protection against sexual transmission of HIV-1. (C) 1998 Academic Press.