Genetic characterization of an atypical Schmallenberg virus isolated from the brain of a malformed lamb.

A novel orthobunyavirus, named "Schmallenberg virus" (SBV), was first detected in the blood of cattle at the end of the summer in Germany in 2011, and subsequently in late autumn from the brain of a stillborn malformed lamb in The Netherlands. Full genome sequences, including 5' and 3' terminal "panhandle" sequences of the L, M, and S segments of the SBV isolated from lamb brain tissue (named HL1) were determined. In addition, a second SBV strain was isolated from the blood of a dairy cow (named F6) also in The Netherlands. This isolate was passaged on Vero cells, and its genome sequence was determined by next-generation sequencing. Alignments of the two genome sequences revealed 4, 12, and 2 amino acid differences in the open reading frames of the L, M, and S segments, respectively. Eleven of a total of 12 amino acid differences were detected in the M segment encoding the ectodomain of the putative structural glycoprotein Gc. Notably, in the HL1 isolate, positions 737-739 are occupied by isoleucine, arginine, and leucine (IRL), whereas in the majority of other sequenced SBV isolates these positions are occupied by threonine, histidine, and proline, respectively. Moreover, in all sheep, goat, and cattle SBV isolates sequenced and published so far, an IRL sequence was never found. This has brought us to the conclusion that the M segment of the HL1 isolate differed markedly from that of other lamb and cow isolates. Whether this atypical variant resulted from adaptation to the ewe, fetus, or insect vector remains to be investigated.