A mutation ‘hot spot’ in the Schmallenberg virus M segment

Abstract

In the autumn of 2011, Schmallenberg virus (SBV), a novel orthobunyavirus of the Simbu serogroup, was identified by metagenomic analysis in Germany. SBV has since been detected in ruminants all over Europe, and investigations on phylogenetic relationships, clinical signs and epidemiology have been conducted. However, until now, only comparative sequence analysis of SBV genome segments with other species of the Simbu serogroup have been performed, and detailed data on the S and M segments, relevant for virus-host-cell interaction, have been missing. In this study, we investigated the S-and M-segment sequences obtained from 24 SBVpositive field samples from sheep, cattle and a goat collected from all over Germany. The results obtained indicated that the overall genome variability of SBV is neither regionally nor host species dependent. Nevertheless, we characterized for the first time a region of high sequence variability (a mutation 'hot spot') within the glycoprotein Gc encoded by the M segment.In the autumn of 2011, a new disease was recognized in dairy cattle on a farm near the city of Schmallenberg (North Rhine-Westphalia, Germany). The animals suffered from diarrhoea, fever and a decrease in milk production. Metagenomic analyses conducted at the Friedrich-LoefflerInstitut, Germany, revealed a novel arthropod-borne orthobunyavirus (family Bunyaviridae) of the Simbu serogroup closely related to viruses of the species Sathuperi virus Yanase et al., 2012). The virus was named Schmallenberg virus (SBV) and was later also identified in foetuses of newborn sheep, cattle and goats that displayed congenital malformations and stillbirths (Bilk et al., 2012; reviewed by Beer et al., 2013;Conraths et al., 2013). Continuous investigations of field samples revealed that SBV has spread in Germany along a geographical west-east gradient, as well as in Europe (http://www.fli.bund.de/en/startseite/current-news/ animal-disease-situation/new-orthobunyavirus-detected-incattle-in-germany.html). Exposure to SBV in livestock and wildlife ruminants has been determined to be high . Since the first detection of SBV in 2011, many studies on the seroprevalence (Elbers et al., 2012;Garigliany et al., 2012b;Loeffen et al., 2012), clinical picture and pathology (Herder et al., 2012;Hoffmann et al., 2012;van den Brom et al., 2012), epidemiology Garigliany et al., 2012a) and vectors (de Regge et al., 2012; Rasmussen et al., 2012), and even studies on the nonzoonotic potential of SBV, have been published (Ducomble et al., 2012;Reusken et al., 2012). In addition, a few phylogenetic and comparative full-genome sequence analyses have been conducted using only the original SBV sample (BH80/11-4; Hoffmann et al., 2012) and other members of the Simbu serogroup Yanase et al., 2012). However, to our knowledge, the variability of SBV genomes collected in a regionally restricted area from different host species has not been investigated. Thus, our study concerning SBV genome variability in Germany represents a novel approach.Like all orthobunyavirus...

Analysis of the humoral immune response against the envelope glycoprotein Gc of Schmallenberg virus reveals a domain located at the amino terminus targeted by mAbs with neutralizing activity

“…The most exposed surfaces of such a structural arrangement potently stimulate B-cells via interaction with receptors, resulting in immunogenic domains (reviewed by Schneider-Ohrum & Ross, 2012). Interestingly, a high frequency of mutations has been reported to occur in vitro and in vivo (Coupeau et al, 2013;Fischer et al, 2013) in the domain of Gc that includes SBV Gc Amino. The variability of this region might therefore also be related to the evolution of the virus within the host and to its adaptation to cell culture.…”

“…A total of ten bovine sera were tested (five positive and five negative sera). Also, one bovine hyperimmune serum and one negative serum were used as controls (Wernike et al, 2013). The status of each serum was verified by virus neutralization test as described below and with a commercial ELISA (IDEXX Schmallenberg Ab; IDEXX).…”

“…The volume was then adjusted with buffer W-Tx-100 (buffer W, 0.2 % Triton X-100 (v/v) Virus neutralization test. The test was performed as previously described (Wernike et al, 2013).…”

Time-dependent selection pressure on two arthropod-borne RNA viruses in the same serogroup

“…While AKV is relatively older and has been causing sporadic outbreaks in the cattle industries across Asia, Australia, and Africa since 1970s (Geoghegan et al, 2014;Jun et al, 2012;Kessell et al, 2011;Kono et al, 2008;Lee et al, 2007;Oem et al, 2014Oem et al, , 2012Yamakawa et al, 2006), SBV was first reported in autumn 2011 in Germany (Hoffmann et al, 2012) and subsequently, spread across most of the European countries Chaintoutis et al, 2014;Doceul et al, 2013;Dominguez et al, 2014;Herder et al, 2012;van den Brom et al, 2012;Yilmaz et al, 2014). The two viruses have similar genomic features with three genomic segments, small (S), medium (M) and large (L) (Fischer et al, 2013). While the S segment encodes a small nonstructural protein and the nucleocapsid protein, the L segment encodes the RNA-dependent RNA polymerase (Fischer et al, 2013).…”

“…Akabane virus (AKV) and Schmallenberg virus (SBV) are the arthropod-borne orthobunyavirus (family Bunyaviridae) of the Simbu serogroup (Hoffmann et al, 2012), which primarily affect ruminants and are associated with abortion, stillbirth, premature births and congenital abnormalities (Doceul et al, 2013;Fischer et al, 2013;Hoffmann et al, 2012;Kono et al, 2008;Yamakawa et al, 2006). Although both viruses have similar etiological features and host range, they exhibit distinct geographical distributions and emerge at different time points.…”