LOSS OF ACTIVE NEUROINVASIVENESS IN ATTENUATED STRAINS OF WEST NILE VIRUS - PATHOGENICITY IN IMMUNOCOMPETENT AND SCID MICE

The neuropathogenicity of West Nile virus (WNV) and two derived attenu ated strains WN25 and WN25A, was studied in young adult ICR mice and i n severe combined immunodeficient (SCID) mice. Similarity in serology and RNA fingerprints were found between WNV and WN25. The viral envelo pe proteins of the attenuates differed from WNV in their slower mobili ty in SDS-PAGE due probably to the presence of N-linked glycan. The th ree strains were lethal to ICR mice by intracerebral (IC) inoculation, but when inoculated intraperitoneally (IP), WNV caused viremia, invad ed the CNS and was lethal, whereas the attenuates showed no viremia or invasion of the CNS. The attenuates elicited antibodies to comparable levels as WNV in IP-infected mice, conferring upon them immunity to I C challenge with the wild type. In IP-inoculated SCID mice the three s trains exhibited similar high viremiae that lasted until death of the animals. All strains invaded the CNS and proliferated in the mouse bra in to similar high titers, but differed largely in the time of invasio n: WNV invaded the CNS of SCID mice (and two other mouse strains) much earlier than the attenuates, which showed large intervals in their ti me of invasion into individual mouse brains within the group. The data presented for SCID mice indicate that WN25 and WN25A have truly lost the neuroinvasive property, and that this property materialized by a p rescribed, active process specific for WNV.