A27L protein mediates vaccinia virus interaction with cell surface heparan sulfate.

Abstract

Vaccinia virus has a wide host range and infects mammalian cells of many different species. This suggests that the cell surface receptors for vaccinia virus are ubiquitously expressed and highly conserved. Alternatively, different receptors are used for vaccinia virus infection of different cell types. Here we report that vaccinia virus binds to heparan sulfate, a glycosaminoglycan (GAG) side chain of cell surface proteoglycans, during virus infection. Soluble heparin specifically inhibits vaccinia virus binding to cells, whereas other GAGs such as condroitin sulfate or dermantan sulfate have no effect. Heparin also blocks infections by cowpox virus, rabbitpox virus, myxoma virus, and Shope fibroma virus, suggesting that cell surface heparan sulfate could be a general mediator of the entry of poxviruses. The biochemical nature of the heparin-blocking effect was investigated. Heparin analogs that have acetyl groups instead of sulfate groups also abolish the inhibitory effect, suggesting that the negative charges on GAGs are important for virus infection. Furthermore, BSC40 cells treated with sodium chlorate to produce undersulfated GAGs are more refractory to vaccinia virus infection. Taken together, the data support the notion that cell surface heparan sulfate is important for vaccinia virus infection. Using heparin-Sepharose beads, we showed that vaccinia virus virions bind to heparin in vitro. In addition, we demonstrated that the recombinant A27L gene product binds to the heparin beads in vitro. This recombinant protein was further shown to bind to cells, and such interaction could be specifically inhibited by soluble heparin. All the data together indicated that A27L protein could be an attachment protein that mediates vaccinia virus binding to cell surface heparan sulfate during viral infection.

• Authors: C S Chung, J C Hsiao, Y S Chang, W Chang
• Journal: Journal of virology (J Virol) Vol. 72 Issue 2 Pg. 1577-85 (Feb 1998) ISSN: 0022-538X [Print] United States
• PMID: 9445060 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carrier Proteins
• Glycosaminoglycans
• Receptors, Virus
• Recombinant Proteins
• Viral Structural Proteins

Topics

• Carrier Proteins (physiology)
• Cell Line
• Glycosaminoglycans (physiology)
• Humans
• Receptors, Virus (physiology)
• Recombinant Proteins
• Vaccinia (virology)
• Vaccinia virus (physiology)
• Viral Structural Proteins (physiology)
• Virus Replication