Heparan sulfate proteoglycan is an important attachment factor for cell entry of Akabane and Schmallenberg viruses

Murakami, S., Takenaka-Uema, A., Kobayashi, T., Kato, K., Shimojima, M., Palmarini, M. and Horimoto, T. (2017) Heparan sulfate proteoglycan is an important attachment factor for cell entry of Akabane and Schmallenberg viruses. Journal of Virology, 91(15), e00503-17. (doi: 10.1128/JVI.00503-17) (PMID:28539443)

Abstract

Akabane (AKAV) and Schmallenberg (SBV) viruses are Orthobunyavirus transmitted by arthropod vectors with a broad cellular tropism in vitro as well as in vivo Both AKAV and SBV cause arthrogryposis-hydranencephaly syndrome in ruminants. The main cellular receptor and attachment factor for entry of these orthobunyaviruses are unknown. Here, we found that AKAV and SBV infections were inhibited by the addition of heparin or enzymatic removal of cell surface heparan sulfates. To confirm this finding, we prepared heparan sulfate proteoglycan (HSPG)-knockout (KO) cells by using a CRISPR/Cas9 system and measured the binding quantities of these viruses to cell surfaces. We observed a substantial reduction in AKAV and SBV binding to cells, limiting the infections by these viruses. These data demonstrate that HSPGs are important cellular attachment factors for AKAV and SBV, at least in vitro, to promote virus replication in susceptive cells. Importance: AKAV and SBV are the etiological agents of arthrogryposis-hydranencephaly syndrome in ruminants, which causes considerable economic losses in the livestock industry. Here, we identified heparan sulfate proteoglycan as a major cellular attachment factor for the entry of AKAV and SBV. Moreover, we found that heparin is a strong inhibitor of AKAV and SBV infections. Revealing the molecular mechanisms of virus-host interactions is critical in order to understand virus biology and develop novel live attenuated vaccines.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Palmarini, Professor Massimo
• Authors: Murakami, S., Takenaka-Uema, A., Kobayashi, T., Kato, K., Shimojima, M., Palmarini, M., and Horimoto, T.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Journal Name: Journal of Virology
• Publisher: American Society for Microbiology
• ISSN: 0022-538X
• ISSN (Online): 1098-5514
• Published Online: 24 May 2017
• Copyright Holders: Copyright © 2017 American Society for Microbiology
• First Published: First published in Journal of Virology 91(15):e00503-17
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher