Contents lists available at ScienceDirect Infection, Genetics and Evolution journal homepage: www.elsevier.com/locate/meegid Research paper A novel reassortant mammalian orthoreovirus with a divergent S1 genome segment identified in a traveler with diarrhea Tina Mikuletič a, ⁎ , Andrej Steyer a , Tadeja Kotar b , Tomaž Mark Zorec a , Mario Poljak a a Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Zaloška 4, 1000 Ljubljana, Slovenia b Department of Infectious Diseases, Ljubljana University Medical Center, Japljeva 2, 1000 Ljubljana, Slovenia ARTICLE INFO Keywords: Mammalian orthoreovirus Human Jones strain S1 genome segment Reassortment ABSTRACT Mammalian orthoreoviruses with reassortant genomes have recently been detected in various mammals and humans with respiratory, central nervous system, and gastrointestinal symptoms. This study describes the de- tection of the novel reassortant mammalian orthoreovirus SI-MRV07 in a traveler with gastroenteritis that re- turned from southeast Asia. The virus was initially detected with electron microscopy in stool, followed by propagation in the epithelial-like monkey kidney Marc145 cell line. Whole-genome sequencing revealed the reassortant nature of the genome segments, whereby the S1 genome segment was the most variable according to known sequences deposited in GenBank. Based on the nucleotide sequence of the S1 genome segment, the isolate clusters to serotype 2, close to the reference strain Jones T2J. The patient's serum showed the highest virus neutralization capacity toward SI-MRV07 and T2J isolates. This study provides additional insight into emerging mammalian orthoreoviruses with reassortant genomes and possible zoonotic potential, which should be care- fully monitored in the future. 1. Introduction Mammalian orthoreoviruses (MRVs) were first detected in the 1950s in human respiratory and gastrointestinal tracts, although they are rarely associated with severe medical conditions (Sabin, 1959). Since then, several studies have been carried out to determine the clinical importance of MRVs in humans. MRVs have been generally recognized as respiratory and enteric orphan viruses. MRV ser- oprevalence correlates with age, and already amounts to up to 50% in 5-year-old children (Lerner et al., 1962; Leers and Rozee, 1966; Tai et al., 2005). MRVs are double-layered non-enveloped viruses, and thus relatively stable in the environment, allowing not only person-to-person infection, but also indirect infection with contaminated food, water, or surfaces. MRVs are often present in wastewater, and they are commonly used as surrogates to determine fecal pollution of surface or ground- water (Betancourt and Gerba, 2016). The presence of MRVs in waste- water, as well as the possibility of indirect transmission and infection, might explain the high seroprevalence already observed in early childhood. Mammalian orthoreoviruses are double-stranded viruses with a segmented genome. The whole genome consists of 10 segments, which are designated as large (L, three segments), medium (M, three segments), or small (S, four segments) based on their electrophoretic mobility (Nibert et al., 1990). Neutralization and hemagglutinin ac- tivities are restricted to the S1 genome segment (Weiner and Fields, 1977), which encodes the outermost glycoprotein σ1. This is re- sponsible for viral attachment to cellular receptors, and it defines the MRV serotype (Lee et al., 1981). Within the S1 open reading frame (ORF) most of the MRV strains possess another shorter and shifted ORF that encodes the non-structural σ1s protein. The expression of σ1s has been shown to be an important factor in viral pathogenesis (Boehme et al., 2009; Boehme et al., 2011). Having segmented genomes, MRVs can reassort their genomes during coinfections. This is evident from detailed molecular studies, reporting highly divergent and reassortant reovirus strains (Steyer et al., 2013; Lelli et al., 2015; Thimmasandra Narayanappa et al., 2015; Feher et al., 2017). Moreover, MRVs have been found in almost all mammals studied, and many MRVs can cross the species barrier, resulting in a constant source of zoonotic viruses with a potential threat to humans. Although generally considered bystanders, there have been some recent reports on reovirus infections in animals and humans associated with severe clinical presentations, mainly related to the respiratory, enteric, and central nervous systems (Decaro et al., 2005; Ouattara et al., 2011; Steyer et al., 2013; Thimmasandra Narayanappa et al., https://doi.org/10.1016/j.meegid.2019.06.002 Received 14 November 2018; Received in revised form 1 June 2019; Accepted 3 June 2019 ⁎ Corresponding author at: Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Zaloška cesta 4, SI-1000 Ljubljana, Slovenia. E-mail addresses: tina.mikuletic@mf.uni-lj.si (T. Mikuletič), andrej.steyer@mf.uni-lj.si (A. Steyer), tadeja.kotar@kclj.si (T. Kotar), tomaz-mark.zorec@mf.uni-lj.si (T.M. Zorec), mario.poljak@mf.uni-lj.si (M. Poljak). Infection, Genetics and Evolution 73 (2019) 378–383 Available online 05 June 2019 1567-1348/ © 2019 Published by Elsevier B.V. T