PMID: 11329179May 1, 2001Paper

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

Glia
A BoutetMarc Tardieu

Abstract

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-1beta (CCR5-agonist), SDF-1alpha (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 a...Continue Reading

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Citations

Sep 26, 2008·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Nazira El-HageKurt F Hauser
Oct 24, 2007·Molecular Neurobiology·A H de HaasK P H Biber
Jun 27, 2006·AIDS Research and Human Retroviruses·M Sarah HillEdward B Stephens
Dec 15, 2005·Journal of Virology·Deborah Carroll-Anzinger, Lena Al-Harthi
Feb 9, 2017·Cell Reports·Rebecca A RussellQuentin J Sattentau
Dec 3, 2014·Microbial Pathogenesis·Ashok Chauhan, Mehrab Khandkar
Apr 15, 2009·Journal of Neuroscience Research·Wei KouAnuja Ghorpade
Aug 10, 2011·Journal of Neuroscience Research·Tamima AshrafReina Bendayan
Nov 19, 2015·Frontiers in Microbiology·Kathleen Borgmann, Anuja Ghorpade

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