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Isolated human astrocytes are not susceptible to infection by M‐ and T‐tropic HIV‐1 strains despite functional expression of the chemokine receptors CCR5 and CXCR4
Author(s) -
Boutet Agnès,
Salim Hassan,
Taoufik Yassine,
Lledo PierreMarie,
Vincent JeanDidier,
Delfraissy JeanFrançois,
Tardieu Marc
Publication year - 2001
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.1051
Subject(s) - biology , chemokine receptor , ccr3 , microglia , chemokine receptor ccr5 , chemokine , astrocyte , neuroglia , cxcr4 , receptor , c c chemokine receptor type 6 , microbiology and biotechnology , cc chemokine receptors , immunology , virology , inflammation , central nervous system , biochemistry , neuroscience
Within the brain, HIV‐1 targets the microglia and astrocytes. Previous studies have reported that viral entry into astrocytes is independent of CD4, in contrast to microglia. We aimed to determine whether chemokine receptors play a role in mediating CD4‐independent HIV‐1 entry into astrocytes. We found that embryonic astrocytes and microglial cells express CCR5, CCR3, and CXCR4 transcripts. Intracellular calcium levels in astrocytes were found to increase following application of RANTES, MIP‐1β (CCR5‐agonist), SDF‐1α (CXCR4‐agonist), but not eotaxin (CCR3‐agonist). In microglial cells, eotaxin was also able to modulate internal calcium homeostasis. CD4 was not present at the cell surface of purified astrocytes but CD4 mRNA could be detected by RT‐PCR. Neither HIV‐1 9533 (R5 isolate) nor HIV‐1 LAI (X4 isolate) penetrated into purified astrocytes. In contrast, mixed CNS cell cultures were infected by HIV‐1 9533 and this was inhibited by anti‐CD4 mAb in 4/4 tested cultures and by anti‐CCR5 mAb in 2/4. Thus, the HIV‐1 R5 strain requires CD4 to penetrate into brain cells, suggesting that CCR5 cannot be used as the primary receptor for M‐tropic HIV‐1 strains in astrocytes. Moreover, inconstant inhibition of HIV‐1 entry by anti‐CCR5 mAb supports the existence of alternative coreceptors for penetration of M‐tropic isolates into brain cells. GLIA 34:165–177, 2001. © 2001 Wiley‐Liss, Inc.