Antigenic Relationships Among Certain Arthropod-Borne Viruses As Revealed by Neutralization Tests
Authors: Smithburn K. C. 
Published: January 2023

Summary
The problem of interrelationships among arthropod-borne viruses which are neurotropic for Swiss mice was attacked from 4 avenues of approach.
Cross-neutralization tests with univalent laboratory-produced monkey antisera and 23 different viruses yielded evidence of numerous interrelationships involving 14 of the viruses. Some of these relationships have not been recorded previously. A very limited experience with bivalent monkey antisera indicates that the inoculation of a virus into an animal already immune to a related agent may evoke a complex antibody response with: Formation of antibody to the second virus inoculated. Increased antibody to the first virus inoculated. The formation of antibody which is crossreactive with heterologous but related viruses. Analysis of data derived from surveys in which sera from residents of East Africa, Egypt, India, Malaya, and Borneo were tested against a number of different viruses, and in which numerous sera were found to be protective against more than one virus, revealed the following: Many sera which are protective against more than one virus almost certainly possess this capacity as a result of infection with different viruses. Sera which neutralize Ntaya virus are in some countries (Egypt, for example) very frequently protective against West Nile virus; in other countries (Malaya and Borneo being examples) Ntaya-protective sera almost invariably neutralize Japanese B. Sera protective against West Nile or Japanese B are frequently nonprotective against Ntaya, yet the association of one or the other of the former with Ntaya is so frequently observed as to give indication that protection against the latter is sometimes a result of infection with another virus. Sera which neutralize Japanese B virus commonly also neutralize both Murray Valley and West Nile; sera which neutralize Murray Valley frequently neutralize Japanese B and almost invariably neutralize West Nile. A test showing neutralization of 50 LD50 of West Nile or Murray Valley virus is not sufficient to rule out the possibility that the reactive antibody may have been evoked by Japanese B virus. Convalescent sera from established cases of St. Louis, Murray Valley, and Japanese B infections were tested against these 3 and 7 other viruses by sensitive methods calculated to detect cross-reactive antibody if such were present. The Murray Valley sera cross-reacted only with Japanese B virus to such extent as to give rise to possible confusion in diagnostic or survey tests. St. Louis encephalitis convalescent sera were weakly cross-reactive with several viruses; cross-neutralization quantitatively sufficient to give rise to protection in a survey-type test was exhibited by some St. Louis sera against dengue 1, dengue 2, West Nile, and Ntaya viruses. Five St. Louis sera reacted more strongly with heterologous agents than with the homologous. This may indicate ready availability or abundance of group-specific antigen in St. Louis virus and/or low antigenic potency of the typespecific antigen(s). It may also indicate multiple infections. Japanese B encephalitis convalescent sera were strongly protective against the homologous virus and almost invariably strongly crossreactive with both Murray Valley and Ntaya viruses. Cross-reactions of sufficient magnitude to occasion protection in survey tests were occasionally obtained with dengue 1, West Nile, Ilhéus, and Uganda S viruses.
The cross-reactions with Japanese B encephalitis convalescent sera and Murray Valley virus were doubtless occasioned by the close antigenic relationship of these 2 viruses. The possibility cannot be ruled out that some or all of the other strong cross-reactions with encephalitis convalescent sera were due to the donors having had experience with the viruses concerned.