title: Heparin binds to murine leukemia virus and inhibits Env-independent attachment and infection.
abstract: Certain glycosaminoglycans (GAGs), including heparin, inhibit infection by murine leukemia virus (MLV). We now show that this is due to inhibition of virus attachment independent of the interaction between viral envelope proteins (Env) and their cellular receptors. Heparin blocked the binding of both Env-deficient and amphotropic MLV (MLV-A) particles to NIH 3T3 fibroblasts, CHO cells which lack the amphotropic retroviral receptor Pit-2, and CHO cells transfected with Pit-2 (CHO-Pit-2). Heparin also inhibited the transduction of NIH 3T3 cells by MLV-A over a similar concentration range. This effect was observed within 15 min of exposure to retrovirus. Preloading target cells with heparin had no effect on transduction and both MLV-A and Env-deficient retrovirus bound efficiently to heparin-coated agarose beads, suggesting that heparin interacts with the virus rather than the target cell. This requires both a strong negative charge and a specific structure since GAGs with different charge and carbohydrate composition inhibited virus infection variably. The specificity of GAG-virus interaction also depends on the producer cells, since virus packaged by murine GP+EnvAM12 cells was 1,000-fold more sensitive to inhibition by chondroitin sulfate A than was virus packaged by human FLYA13 packaging cells. No evidence for an interaction between MLV and cell surface proteoglycans was found, however, since the attachment of MLV-A and envelope-defective virus to proteoglycan-deficient CHOpgsA-745 cells was similar to that seen with both wild-type and CHO-Pit-2 cells. Although the molecular mechanism is unclear, this study presents evidence that Env receptor-independent attachment is an important step in MLV infection.
authors.affiliation: Department of Haematology, University College, London, United Kingdom.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Walker
authors.forename: Massimo
authors.initials: M
authors.lastname: Pizzato
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Takeuchi
authors.forename: Stephen
authors.initials: S
authors.lastname: Devereux
mesh_terms: D016475:3T3 Cells; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D015686:Gene Products, env / Q000235:genetics / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000378:metabolism; D006493:Heparin / Q000378:metabolism* / Q000494:pharmacology; D009052:Leukemia Virus, Murine / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D051379:Mice; D011991:Receptors, Virus / Q000378:metabolism*; D014161:Transduction, Genetic
chemical_list: D015686:Gene Products, env; D006025:Glycosaminoglycans; D011991:Receptors, Virus; D006493:Heparin