Binding of Sindbis Virus to Cell Surface Heparan Sulfate

Abstract

Alphaviruses are arthropod-borne viruses with wide species ranges and diverse tissue tropisms. The cell surface receptors which allow infection of so many different species and cell types are still incompletely characterized. We show here that the widely expressed glycosaminoglycan heparan sulfate can participate in the binding of Sindbis virus to cells. Enzymatic removal of heparan sulfate or the use of heparan sulfate-deficient cells led to a large reduction in virus binding. Sindbis virus bound to immobilized heparin, and this interaction was blocked by neutralizing antibodies against the viral E2 glycoprotein. Further experiments showed that a high degree of sulfation was critical for the ability of heparin to bind Sindbis virus. However, Sindbis virus was still able to infect and replicate on cells which were completely deficient in heparan sulfate, indicating that additional receptors must be involved. Cell surface binding of another alphavirus, Ross River virus, was found to be independent of heparan sulfate.

Murine encephalitis caused by HCoV-OC43, a human coronavirus with broad species specificity, is partly immune-mediated

“…While little is known about the changes required for efficient replication of HCoV-OC43 in the murine CNS, it is likely that this process includes mutations that affect binding to host cell sugar moieties. Infection with the prototypic alphavirus, Sindbis virus (SINV), or with a picornavirus, Theiler's murine encephalomyelitis virus (TMEV), is initiated by binding to a polyanionic polysaccharide, heparin sulfate (Byrnes and Griffin, 1998;Klimstra et al, 1998;Reddi and Lipton, 2002). SINV with enhanced binding to heparin sulfate is selected after passage in tissue culture cells.…”

Transmission cycles, host range, evolution and emergence of arboviral disease

“…However, specialization for replication in the hamster host resulted in rapid increases in virus fitness with many mutations, consistent with virus adaptation and evolutionary constraints imposed by the alternating-host cycle of arboviruses 88 . Cell-culture models probably do not fully reflect in vivo conditions, as artefacts (such as selection for virus binding to heparin sulphate) might distort results 89,90 .…”

Evolutionary Influences in Arboviral Disease

“…The inconsistencies in the results described above from different studies suggest limitations in the cell culture model systems used to study arbovirus evolution. In addition, artifactual adaptation events mediated by binding of some arboviruses to unnatural receptors such as glycosaminoglycans (Byrnes and Griffin 1998;Klimstra et al 1998;Hilgard and Stockert 2000), which are found on the surface of both vertebrate and invertebrate cells, suggest that selection conditions in vivo might yield different results and conclusions.…”