Susceptibility of in Vitro Stimulated PBMC to Infection with NSI HIV-1 Is Associated with Levels of CCR5 Expression and β-Chemokine Production

• Published in: Virology (New York, N.Y.) N.Y.), 2000-02, Vol.267 (2), p.237-246
• Main Authors: Blaak, Hetty, Ran, Leonie J., Rientsma, Ronald, Schuitemaker, Hanneke
• Format: Article
• Language: English
• Subjects: AIDS/HIV; CCR5 gene; CCR5 protein; CD4 antigen; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - metabolism; CD8 Antigens - metabolism; Chemokines, CC - metabolism; Genotype; HIV-1 - growth & development; human immunodeficiency virus 1; Humans; Interleukin-2 - pharmacology; Leukocytes, Mononuclear - metabolism; Leukocytes, Mononuclear - virology; Phytohemagglutinins - pharmacology; Receptors, CCR5 - drug effects; Receptors, CCR5 - genetics; Receptors, CCR5 - metabolism; Receptors, Cell Surface - genetics; Receptors, Cell Surface - metabolism; Recombinant Proteins - pharmacology
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1006/viro.1999.0111

Susceptibility of PHA/rIL-2-stimulated PBMC from 14 healthy blood donors for NSI HIV-1 infection was analyzed in relation to CCR5 expression and β-chemokine production. After 1 week of culture in the presence of rIL-2, but not at the moment of inoculation, CCR5 surface expression was positively and β-chemokine production was inversely associated with susceptibility to NSI HIV-1 infection. Surprisingly, no association was observed between CCR5 genotype and in vitro NSI HIV-1 susceptibility, which was in agreement with similar levels of CCR5 surface expression and β-chemokine production in CCR5Δ32/+ and CCR5 +/+ PBMC after PHA/rIL-2 stimulation. In contrast to what was observed in vitro, CCR5 genotype did associate with CCR5 surface expression levels in vivo in resting as well as in activated CD4+ T cell populations that were identified by the expression of CD45RO, CD27, HLA-DR, and CD69. The association between CCR5 expression and susceptibility to infection by NSI HIV-1 observed in vitro might offer an explanation for the in vivo observed protective effect of CCR5 polymorphisms that influence CCR5 expression on disease progression.