Downloaded from www.microbiologyresearch.org by IP: 54.211.192.98 On: Wed, 19 Apr 2017 06:27:36 Acute hantavirus infection induces galectin-3-binding protein Jussi Hepojoki, 1 Tomas Strandin, 1 Udo Hetzel, 2 Tarja Sironen, 1 Jonas Klingstro ¨m, 3 Jussi Sane, 1 Satu Ma ¨ kela ¨, 4,5 Jukka Mustonen, 4,5 Seppo Meri, 6 A ˚ ke Lundkvist, 7 Olli Vapalahti, 1,2,8 Hilkka Lankinen 1 and Antti Vaheri 1,8 Correspondence Jussi Hepojoki jussi.hepojoki@helsinki.fi Received 11 April 2014 Accepted 7 July 2014 1 Department of Virology, Peptide and Protein Laboratory, Haartman Institute, University of Helsinki, Helsinki, Finland 2 Veterinary Pathology, Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, Finland 3 Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska, University Hospital Huddinge, Stockholm, Sweden 4 Department of Internal Medicine, Tampere University Hospital, University of Tampere, Tampere, Finland 5 School of Medicine, University of Tampere, Tampere, Finland 6 Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Helsinki, Finland 7 Swedish Institute for Communicable Disease Control, Solna, Sweden 8 Department of Virology and Immunology, HUSLAB, Hospital District of Helsinki and Uusimaa, Finland Hantaviruses are zoonotic viruses that cause life-threatening diseases when transmitted to humans. Severe hantavirus infection is manifested by impairment of renal function, pulmonary oedema and capillary leakage. Both innate and adaptive immune responses contribute to the pathogenesis, but the underlying mechanisms are not fully understood. Here, we showed that galectin-3-binding protein (Gal-3BP) was upregulated as a result of hantavirus infection both in vitro and in vivo. Gal-3BP is a secreted glycoprotein found in human serum, and increased Gal-3BP levels have been reported in chronic viral infections and in several types of cancer. Our in vitro experiments showed that, whilst Vero E6 cells (an African green monkey kidney cell line) constitutively expressed and secreted Gal-3BP, this protein was detected in primary human cells only as a result of hantavirus infection. Analysis of Gal-3BP levels in serum samples of cynomolgus macaques infected experimentally with hantavirus indicated that hantavirus infection induced Gal-3BP also in vivo. Finally, analysis of plasma samples collected from patients hospitalized because of acute hantavirus infection showed higher Gal-3BP levels during the acute than the convalescent phase. Furthermore, the Gal-3BP levels in patients with haemorrhagic fever with renal syndrome correlated with increased complement activation and with clinical variables reflecting the severity of acute hantavirus infection. INTRODUCTION Hantaviruses (genus Hantavirus, family Bunyaviridae) are rodent- and insectivore-borne viruses that occasionally infect humans causing either haemorrhagic fever with renal syndrome (HFRS; Eurasian hantaviruses) or hantavirus cardiopulmonary syndrome (HCPS; American hanta- viruses) with respective case-fatality rates of 0.1–12 and 30–40 % (Vaheri et al., 2013). Severe cases of HFRS and HCPS are manifested by impairment of renal function, pulmonary oedema and vascular leakage. The mechanisms underlying these clinical signs remain largely unknown. However, involvement of the complement system has been suggested (Sane et al., 2011). The main HFRS-causing viruses include Hantaan virus, Dobrava virus, Seoul virus and Puumala virus (PUUV). HCPS is mainly caused by Sin Nombre and Andes viruses (Jonsson et al., 2010). Tula Journal of General Virology (2014), 95, 2356–2364 DOI 10.1099/vir.0.066837-0 2356 066837 G 2014 The Authors Printed in Great Britain