title: Envelope-dependent, cyclophilin-independent effects of glycosaminoglycans on human immunodeficiency virus type 1 attachment and infection.
abstract: Cell surface glycosaminoglycans (GAGs), in particular heparan sulfate (HS), have been proposed to mediate the attachment of human immunodeficiency virus type 1 (HIV-1) to target cells prior to virus entry, and both the viral gp120 envelope protein and virion-associated cyclophilin A (CypA) have been shown to directly interact with HS and its analogues. To determine the role of GAGs in HIV attachment and infection, we generated HIV-susceptible derivatives of CHO cell lines that either express high levels of GAGs (CHO-K1) or lack GAGs (pgsA745). Using a panel of HIV-1 envelopes, we found that cell surface GAG-mediated effects on virion attachment and infection vary in an envelope strain-dependent but coreceptor-independent manner. In fact, cell surface GAG-mediated enhancement of infection is confined to isolates that contain a highly positively charged V3-loop sequence, while infection by most strains is apparently inhibited by the presence of GAGs. Moreover, the enhancing and inhibitory effects of polycations and polyanions on HIV-1 infection are largely dependent on the presence of cell surface GAGs. These observations are consistent with a model in which GAGs influence in vitro HIV-1 infection primarily by modifying the charge characteristics of the target cell surface. Finally, the effects of GAGs on HIV-1 infection are observed to an equivalent extent whether CypA is present in or absent from virions. Overall, these data exclude a major role for GAGs in mediating the attachment of many HIV-1 strains to target cells via interactions with virion-associated gp120 or CypA.
authors.affiliation: Aaron Diamond AIDS Research Center, Columbia University College of Physicians and Surgeons, New York, New York, USA.
authors.forename: Yi-Jun
authors.initials: YJ
authors.lastname: Zhang
authors.forename: Theodora
authors.initials: T
authors.lastname: Hatziioannou
authors.forename: Trinity
authors.initials: T
authors.lastname: Zang
authors.forename: Douglas
authors.initials: D
authors.lastname: Braaten
authors.forename: Jeremy
authors.initials: J
authors.lastname: Luban
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Goff
authors.forename: Paul D
authors.initials: PD
authors.lastname: Bieniasz
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D021983:Cyclophilins / Q000378:metabolism*; D015686:Gene Products, env / Q000378:metabolism*; D015683:Gene Products, gag / Q000235:genetics / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism*; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000378:metabolism; D015658:HIV Infections / Q000821:virology; D015497:HIV-1 / Q000472:pathogenicity* / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D014771:Virion / Q000472:pathogenicity / Q000502:physiology
chemical_list: D015686:Gene Products, env; D015683:Gene Products, gag; D006025:Glycosaminoglycans; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D021983:Cyclophilins