Donor variation in in vitro HIV-1 susceptibility of monocyte-derived macrophages

被引:44
作者
Bol, Sebastiaan M.
van Remmerden, Yvonne
Sietzema, Jantine G.
Kootstra, Neeltje A.
Schuitemaker, Hanneke
van 't Wout, Angelique B.
机构
[1] Univ Amsterdam, Acad Med Ctr, Landsteiner Lab, Dept Expt Immunol, NL-1105 AZ Amsterdam, Netherlands
[2] Univ Amsterdam, Acad Med Ctr, Ctr Infect Dis & Immun Amsterdam CINIMA, NL-1105 AZ Amsterdam, Netherlands
关键词
HIV-1; Macrophage; Monocyte; Host genetic variation; CCR5; IMMUNODEFICIENCY-VIRUS TYPE-1; ACTIVE ANTIRETROVIRAL THERAPY; BLOOD MONONUCLEAR-CELLS; GENETIC RESTRICTION; CCR5; EXPRESSION; INFECTION; RESISTANCE; AIDS; REPLICATION; PROGRESSION;
D O I
10.1016/j.virol.2009.05.027
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Primary human cells from different donors vary in their susceptibility to in vitro infection with HIV-1. In order to perform genetic analysis to identify host factors that affect HIV-1 susceptibility, it is important that a clear phenotype is defined. Here, we report a standardized method to Study variation for in vitro HIV-1 infection in monocyte-derived macrophages (MDM) from large numbers of individuals. With this assay, HIV-1 susceptibility of MDM from 489 different donors shows more than 3 log variation and a good correlation with the 32 base pair deletion in the CCR5 co-receptor (ccr5 Delta 32 genotype) of the donors. However, in 7 of 12 donors completely resistant to infection with CCR5-using HIV-1, this was not explained by the ccr5 Delta 32 genotype, showing evidence that other host factors are likely to influence HIV-1 replication in MDM. Infections with VSV-G pseudotyped HIV-1 indeed confirmed the existence of post-entry level restrictions in MDM. (C) 2009 Elsevier Inc. All rights reserved.
引用
收藏
页码:205 / 211
页数:7
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