Blockade of chemokine-induced signalling inhibits CCR5-dependent HIV infection in vitro without blocking gp120/CCR5 interaction.
BACKGROUND
Cellular infection with human immunodeficiency virus (HIV) both in vitro and in vivo requires a member of the chemokine receptor family to act as a co-receptor for viral entry. However, it is presently unclear to what extent the interaction of HIV proteins with chemokine receptors generates intracellular signals that are important for productive infection.


RESULTS
In this study we have used a recently described family of chemokine inhibitors, termed BSCIs, which specifically block chemokine-induced chemotaxis without affecting chemokine ligands binding to their receptors. The BSCI termed Peptide 3 strongly inhibited CCR5 mediated HIV infection of THP-1 cells (83 +/- 7% inhibition assayed by immunofluoresence staining), but had no effect on gp120 binding to CCR5. Peptide 3 did not affect CXCR4-dependent infection of Jurkat T cells.


CONCLUSIONS
These observations suggest that, in some cases, intracellular signals generated by the chemokine coreceptor may be required for a productive HIV infection.
Grainger
David J
DJ
Department of Medicine, University of Cambridge, Box 157, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 2QQ, UK. djg15@cam.ac.uk
Lever
Andrew M L
AM
D002460:Cell Line; D018925:Chemokines / Q000494:pharmacology*; D002633:Chemotaxis; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D015497:HIV-1 / Q000187:drug effects* / Q000472:pathogenicity*; D006801:Humans; D019169:Jurkat Cells; D008264:Macrophages / Q000821:virology; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology; D019713:Receptors, CCR5 / Q000378:metabolism*; D015728:Receptors, HIV / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
D018925:Chemokines; D015699:HIV Envelope Protein gp120; D010455:Peptides; D019713:Receptors, CCR5; D015728:Receptors, HIV