Virus Research 123 (2007) 19–29 Asymptomatic circulation of HEV71 in Norway Elisabet Witsø a,1 , Gustavo Palacios b,∗,1 , Kjersti S. Rønningen a , Ondrej Cinek c , Diana Janowitz b , Marian Rewers d , Bjørn Grinde a , W. Ian Lipkin b a Norwegian Institute of Public Health, Oslo, Norway b Jerome L. and Dawn Greene Infectious Disease Laboratory, Mailman School of Public Health, Columbia University, 722 West 168th Street, New York, NY 10032, USA c Motol University Hospital, Charles University Prague, Prague, Czech Republic d Barbara Davis Center for Diabetes Research, University of Colorado Health Sciences Center, USA Received 16 May 2006; received in revised form 25 July 2006; accepted 26 July 2006 Available online 11 September 2006 Abstract Widespread circulation of human enterovirus 71 was discovered in a prospective study of fecal samples obtained from healthy Norwegian children. Molecular characterization of the virus determined that it belonged to genotype C1. Complete sequencing of this strain, HEV71 804/NO/03, revealed differences in the 5 ′ UTR and polymerase with respect to more pathogenic genotypes that may explain its reduced neurovirulence. Published by Elsevier B.V. Keywords: Enterovirus 71; Epidemiology; Molecular typing Human enterovirus 71 (HEV71) is associated with outbreaks of hand-foot-and-mouth disease (HFMD), aseptic meningitis and encephalitis. Like poliovirus, HEV71 has affinity for ante- rior horn cells (Chumakov et al., 1979) and is the most common non-polio enterovirus associated with poliomyelitis-like paral- ysis (Melnick, 1984). Since its initial isolation in California in 1969, HEV71 has caused epidemics in Australia, Europe, Asia, and the United States (Palacios and Oberste, 2005). More recently, HEV71 caused brain-stem encephalitis during HFMD outbreaks in Malaysia, in 1997 (Cardosa et al., 2003; Chan et al., 2000) and in Taiwan in 1998 (Ho et al., 1999; Lin et al., 2003). The molecular epidemiology of HEV71 has been widely studied (Brown et al., 1999; Cardosa et al., 2003; Chu et al., 2001; Herrero et al., 2003; McMinn et al., 2001; Shimizu et al., 2004). There are two major HEV71 genogroups (B and C) co-circulating worldwide (the HEV71 prototype strain BrCr, iso- lated in 1969, is the only known example of genogroup A). Genogroups B and C have been subdivided into genotypes: B1–B5 and C1–C4, respectively (Brown et al., 1999; Cardosa et al., 2003; McMinn et al., 2001; Mizuta et al., 2005). Here we ∗ Corresponding author. Fax: +1 212 342 9044 47. E-mail address: gp2050@columbia.edu (G. Palacios). 1 These authors contributed equally to this work. report asymptomatic circulation of HEV71 in Norway. Phylo- genetic analysis of VP1 sequences revealed a single circulating strain of genotype C1. Stool samples were obtained on a monthly basis from 113 healthy infants (60 males, 53 females) in a prospective cohort study focused on environmental triggers of type 1 diabetes. New- borns (6 weeks old) were recruited at their first visit to health care centres. Stool samples and clinical data were obtained monthly from September 2001 to November 2003 (Cinek et al., 2006), beginning at age 3 months and continuing up to 28 months. Total nucleic acids were extracted and analyzed for human enterovirus (HEV) RNA using real-time PCR; 11.3% were positive (Cinek et al., 2006). The serotype of the HEV positive samples (145/1255) were determined by VP1 nucleotide sequencing. HEV71 was detected in 16.8% (19/113) of the children in the cohort (10 boys and 9 girls, median age 14.0 months, 75% <18 months old). Posi- tive samples were detected from children residing in the fol- lowing counties: Akershus (south-east), Nord-Trøndelag (cen- tral) and Hordaland (west coast). This finding suggests a wide geographical distribution. VP1-2A sequences of HEV71 Nor- wegian strains (200–630 nt in length) were deposited in the GenBank under accession numbers DQ317216, DQ317217, DQ317218, DQ317219, DQ317220, DQ317221, DQ317222, DQ317223, DQ317224, DQ317225, DQ317226, DQ317227, 0168-1702/$ – see front matter. Published by Elsevier B.V. doi:10.1016/j.virusres.2006.07.015