Title: Effect of polyanion-resistance on HIV-1 infection
Authors: Bobardt, Michael D ×
Armand-Ugón, Mercedes
Clotet, Imma
Zhang, Zhe
David, Guido
Este, Jose A
Gallay, Philippe A #
Issue Date: Aug-2004
Publisher: Academic Press
Series Title: Virology vol:325 issue:2 pages:389-398
Abstract: Polyanions are potent HIV-1 entry inhibitors. Nevertheless, resistant viruses may emerge under polyanion inhibitory pressure. Specifically, a polyanion-resistant virus replicates in T cells even in the presence of high concentrations of polyanions. We found that although the polyanion-resistant virus grows in suspension CD4+ T cells efficiently, it infects nonlymphocytic adherent CD4+ cells poorly. Given that a main distinction between suspension and adherent cells is the absence or presence of cell-surface heparan sulfate proteoglycan (HSPG), we investigated if the failure of the polyanion-resistant virus to infect adherent CD4+ cells arises from its inability to bind HSPG. We found that the emergence of mutations in gp120 associated with polyanion resistance resulted in a decreased capacity of HIV-1 to bind HSPG. We also found that the polycation polybrene rescued the capacity of the polyanion-resistant virus to bind HSPG and to infect adherent CD4+ cells. The identification of this virus, unable to bind HSPG, provides a convenient probe to measure the impact of HIV-1-HSPG interactions in vivo. Altogether, these findings suggest that polyanion-resistance narrows the range of potential target cells for HIV-1 in the host. This reinforces the hypothesis that cell-free or cell-associated polyanions such as HSPG possess the capacity to modulate HIV-1 pathogenesis.
ISSN: 0042-6822
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular Genetics Section (-)
Department of Human Genetics - miscellaneous
× corresponding author
# (joint) last author

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