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

Abstract 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 t...

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Bibliographic Details
Published in:Virology (New York, N.Y.) N.Y.), 2009-08, Vol.390 (2), p.205-211
Main Authors: Bol, Sebastiaan M, van Remmerden, Yvonne, Sietzema, Jantine G, Kootstra, Neeltje A, Schuitemaker, Hanneke, van 't Wout, Angélique B
Format: Article
Language:English
Subjects:
Adult
CCR5
Cells, Cultured
Female
Genetic Predisposition to Disease
Genetic Variation
HIV-1
HIV-1 - growth & development
HIV-1 - immunology
Host genetic variation
Human immunodeficiency virus 1
Humans
Infectious Disease
Macrophage
Macrophages - immunology
Macrophages - virology
Male
Middle Aged
Monocyte
Receptors, CCR5 - genetics
Sequence Deletion
Young Adult
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Summary:Abstract 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 Δ32 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 Δ32 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.
ISSN:0042-6822
1096-0341
DOI:10.1016/j.virol.2009.05.027