Coreceptor ligand inhibition of fetal brain cell infection by HIV type 1.
The capacity of a panel of HIV-1 isolates to infect primary mixed fetal brain cell cultures was estimated and their sensitivity to inhibition by a range of coreceptor ligands assessed. Our results show that (1) HIV-1 strains that predominantly use CCR5 or only CXCR4 are able to infect microglia in primary brain cell cultures, and (2) ligands to these two coreceptors can inhibit brain cell infection. CCR5 ligands (including AOP-RANTES, a potent inhibitor of CCR5-dependent infection), however, blocked infection only weakly, raising the possibility that alternative unidentified coreceptors are also used. Interestingly, vMIP-II, a chemokine encoded by the Kaposi sarcoma-associated herpes virus (KSHV), reduced brain cell infection by all HIV-1 strains tested, including both R5 and X4 viruses. Our results therefore indicate that novel drugs targeted to the major HIV-1 coreceptors will influence HIV replication in the brain, if they cross the blood-brain barrier.
Hibbitts
S
S
Section of Virology, Chester Beatty Laboratories, Institute of Cancer Research, London, UK.
Reeves
J D
JD
Simmons
G
G
Gray
P W
PW
Epstein
L G
LG
Schols
D
D
de Clercq
E
E
Wells
T N
TN
Proudfoot
A E
AE
Clapham
P R
PR
D019380:Anti-HIV Agents / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000201:enzymology* / Q000821:virology*; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000031:analogs & derivatives / Q000494:pharmacology; D018925:Chemokines / Q000494:pharmacology; D015497:HIV-1 / Q000378:metabolism / Q000472:pathogenicity*; D006801:Humans; D008024:Ligands; D017628:Microglia / Q000821:virology; D019713:Receptors, CCR5 / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism*
D019380:Anti-HIV Agents; D018946:Chemokine CCL5; D018925:Chemokines; D008024:Ligands; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; C111989:aminooxypentane-RANTES; C108059:vMIP-II