Antigenic Variation among Members of the Tick-borne Encephalitis Complex

Abstract

SUMMARYThe antigenic relationships between seven members of the tick-borne encephalitis complex of flaviviruses (group B arboviruses) were examined by raising a library of 16 monoclonal antibodies against one of them and examining their biological and antigenic properties. These clones reacted with only one of two intracellular, virusspecific polypeptides. One polypeptide [mol. wt. 58 × 103 (58K)] is related to the major envelope protein E, but the identity of the other is at present unknown, even though it is a major immunogen in experimental infections and vaccinations. Only those clones specific for the 58K polypeptide contain either neutralizing or haemagglutinininhibiting activity, but these epitopes are not identical. In general, epitopes on the 51K polypeptide were more heavily conserved than those on the 58K polypeptide, although both conserved and variant epitopes were found on both polypeptides. One epitope was present on the 51K polypeptide which was conserved on all seven isolates studied and another epitope on the same polypeptide was specific for all the western isolates including one isolate of louping-ill virus. Using the monoclonal antibodies raised in the study, it was shown that louping-ill virus was closely related antigenically to isolates of the Western subtype of tick-borne encephalitis virus.

Immunological basis for protection in a murine model of tick-borne encephalitis by a recombinant adenovirus carrying the gene encoding the NS1 non-structural protein.

“…In addition, Rad51 gave good levels of protection against infection with Omsk haemorrhagic fever virus, although only low levels of protection were observed after challenge with Negishi virus. The poor protection against Negishi virus infection appears to conflict with our earlier observations (Stephenson et al, 1984) and those of several other workers which show good antigenic homogeneity between TBEVs and louping ill viruses. The E genes of Negishi virus and louping ill virus have been shown by Venugopal et al (1992) to be very closely related and therefore higher levels of cross-protection would have been predicted.…”

“…TBEV was grown in suckling mice brains as described previously (Stephenson et al, 1984). TBEV isolate ' 205 ' was a gift from M. Vorobyova (Tarasevich State Institute, Moscow), Omsk haemorrhagic fever virus (OHFV) was a gift from V. Pogodina (IPVE, Moscow) and Negishi virus was a generous gift from A. Karavanov (IPVE, Moscow) ; all other virus isolates were from the virus collection of the Chumakov Institute of Poliomyelitis and Viral Encephalitides (IPVE) and have been described elsewhere (Stephenson et al, 1984 ;Krasilnikov et al, 1984 ;Dzhivanyan et al, 1988). The recombinant adenoviruses Rad51 (containing the NS1 gene from TBE virus) and Rad35 (containing the β-galactosidase gene from Escherichia coli) were propagated in 293 cells as described previously (Jacobs et al, 1992 ;Wilkinson & Akrigg, 1992).…”

The NS1 protein of tick-borne encephalitis virus forms multimeric species upon secretion from the host cell

“…Viral ELISA antigens were produced in primary avian fibroblasts as described previously and monoclonal antibodies were derived and purified as described by Stephenson et al (1984). ELISA was performed and titres calculated as described previously (Warnes et al, 1994).…”

Sequencing and antigenic studies of a Norwegian virus isolated from encephalomyelitic sheep confirm the existence of louping ill virus outside Great Britain and Ireland

“…receptor binding, neuropathogenicity, membrane fusion, and inducing protective antibody responses (for reviews, see Heinz, 1986;Gould et al, 1990). Antibodies against the E protein have also been used to investigate the interrelationships of the flaviviruses (de Madrid & Porterfield, 1974;Stephenson et al, 1984;Gould et al, 1985b;Calisher et al, 1989;Heinz et al, 1990).…”

“…Monoclonal antibodies (MAbs) generated against central European encephalitis virus have been used to (Stephenson et al, 1984). In this paper, we have used serological analysis, pathogenicity characteristics and nucleotide sequencing of the viral E glycoproteins to compare the relationship of a Norwegian strain of LIlike virus with four Scottish strains of recognized LI virus.…”