Donor variation in in vitro HIV-1 susceptibility of monocyte-derived macrophages.
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.
Bol
Sebastiaan M
SM
Department of Experimental Immunology, Sanquin Research, Landsteiner Laboratory and Center for Infectious Diseases and Immunity Amsterdam (CINIMA), Academic Medical Center of The University of Amsterdam, Amsterdam, The Netherlands.
van Remmerden
Yvonne
Y
Sietzema
Jantine G
JG
Kootstra
Neeltje A
NA
Schuitemaker
Hanneke
H
van't Wout
Angélique B
AB
D000328:Adult; D002478:Cells, Cultured; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D015497:HIV-1 / Q000254:growth & development* / Q000276:immunology; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D019713:Receptors, CCR5 / Q000235:genetics; D017384:Sequence Deletion; D055815:Young Adult
D019713:Receptors, CCR5