TY - JOUR
T1 - Donor variation in in vitro HIV-1 susceptibility of monocyte-derived macrophages
AU - Bol, Sebastiaan M.
AU - van Remmerden, Yvonne
AU - Sietzema, Jantine G.
AU - Kootstra, Neeltje A.
AU - Schuitemaker, Hanneke
AU - van 't Wout, Angélique B.
PY - 2009/8/1
Y1 - 2009/8/1
N2 - 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.
AB - 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.
KW - CCR5
KW - HIV-1
KW - Host genetic variation
KW - Macrophage
KW - Monocyte
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U2 - 10.1016/j.virol.2009.05.027
DO - 10.1016/j.virol.2009.05.027
M3 - Article
C2 - 19535121
AN - SCOPUS:67650045749
SN - 0042-6822
VL - 390
SP - 205
EP - 211
JO - Virology
JF - Virology
IS - 2
ER -