Tahyna virus genetics, infectivity, and immunogenicity in mice and monkeys

Abstract

BackgroundTahyna virus (TAHV) is a human pathogen of the California encephalitis virus (CEV) serogroup (Bunyaviridae) endemic to Europe, Asia, and Africa. TAHV maintains an enzootic life cycle with several species of mosquito vectors and hares, rabbits, hedgehogs, and rodents serving as small mammal amplifying hosts. Human TAHV infection occurs in summer and early fall with symptoms of fever, headache, malaise, conjunctivitis, pharyngitis, and nausea. TAHV disease can progress to CNS involvement, although unlike related La Crosse virus (LACV), fatalities have not been reported. Human infections are frequent with neutralizing antibodies present in 60-80% of the elderly population in endemic areas.ResultsIn order to determine the genomic sequence of wild-type TAHV, we chose three TAHV isolates collected over a 26-year period from mosquitoes. Here we present the first complete sequence of the TAHV S, M, and L segments. The three TAHV isolates maintained a highly conserved genome with both nucleotide and amino acid sequence identity greater than 99%. In order to determine the extent of genetic relatedness to other members of the CEV serogroup, we compared protein sequences of TAHV with LACV, Snowshoe Hare virus (SSHV), Jamestown Canyon virus (JCV), and Inkoo virus (INKV). By amino acid comparison, TAHV was most similar to SSHV followed by LACV, JCV, and INKV. The sequence of the GN protein is most conserved followed by L, N, GC, NSS, and NSM. In a weanling Swiss Webster mouse model, all three TAHV isolates were uniformly neurovirulent, but only one virus was neuroinvasive. In rhesus monkeys, the virus was highly immunogenic even in the absence of viremia. Cross neutralization studies utilizing monkey immune serum demonstrated that TAHV is antigenically distinct from North American viruses LACV and JCV.ConclusionsHere we report the first complete sequence of TAHV and present genetic analysis of new-world viruses, LACV, SSHV, and JCV with old-world viruses, TAHV and INKV. Using immune serum generated in monkeys against TAHV, LACV, and JCV, we have demonstrated cross-neutralization within the CEV serogroup. Such cross reactivity may complicate virus identification, especially following JCV infection which elicited antibodies that cross neutralized both LACV and TAHV. These data also suggest that a single vaccine could generate a cross-neutralizing antibody response which may provide protection against CEV serogroup viruses from a wide geographic range.

A Recombinant Chimeric La Crosse Virus Expressing the Surface Glycoproteins of Jamestown Canyon Virus Is Immunogenic and Protective against Challenge with either Parental Virus in Mice or Monkeys

“…We have previously demonstrated that JCV infection generates a neutralizing antibody response that also efficiently neutralizes both LACV and TAHV viruses (3,4). In the current study, we found that immunization with rJCV/LACV protected mice against lethal challenge with JCV, LACV, or TAHV.…”

“…We have previously reported that infection of rhesus monkeys with JCV results in a strong cross-neutralizing antibody response effective against JCV, LACV, and TAHV that was not observed following infection with LACV or TAHV (3). As a first step in vaccine development, we sought to generate a recombinant LACV virus (rLACV) that expresses the G N and G C glycoproteins of JCV, which should induce neutralizing antibodies against JCV, LACV, and TAHV.…”

Seroprevalence of Schmallenberg virus and other Simbu group viruses among the Lebanese sheep

“…Thus constituting the first occurrence of indigenous circulation of Orthobunyavirus of the serogroup Simbu in Western Europe. However, other Orthobunyavirus were identified in Europe (case of the Batai virus in Germany), Africa, Asia, the Middle East, and Australia (cases of Akabane virus), either sporadically by the analysis of pools of mosquitos (Jöst et al, 2011;Horne and Vanlandingham, 2014), or due to an endemic presence (case of the Tahyna virus) (Bennett et al, 2011). In fact, back in 1980 an outbreak of Akabane virus was confirmed in cattle in the Turkish Province of Aydin.…”

Circulation of Diverse Genotypes of Tahyna Virus in Xinjiang, People's Republic of China

“…Identities for virus isolates from Xinjiang were much lower than those for virus isolates from Europe. 6,7 Also, identities between virus isolates from Xinjiang and Europe were much lower than those within each group ( Supplementary Table 1 ).…”

“…5 Previous studies identified a high level of conservation of the TAHV genome, even though viruses were obtained from temporally distinct regions over a long period. 6,7 In 2006, TAHV was isolated for the first time in the People's Republic of China, and human infection has been confirmed in this country. 8,9 The first TAHV isolate (XJ0625) from China was obtained from Culex sp.…”