Twenty strains of Colorado tick fever (CTF) virus, isolated from ticks, mammals and humans, and two antigenic relatives of CTF virus were compared in cross-neutralization tests. Viruses were tested using single-inoculation sera prepared in hamsters. Antigenic variation, as measured by differences detected in the neutralization test, was noted among the virus isolates identified as strains of CTF virus. The virus strains isolated from humans appeared to vary the most in serological reactions. The two antigenic relatives of CTF virus are clearly distinct from strains of CTF and are different from each other. Antigenic relationships between these two viruses were established using two sets of single-inoculation antisera and both complement fixation and neutralization tests. Six distinct antigenic variants of CTF virus isolated from humans and the virus strain from ticks (75V1906) that showed the least antigenic variation, were tested against 49 coded serum pairs from clinically diagnosed cases of CTF. Significant differences were noted in the number of convalescent-phase sera that reacted with each virus strain and in the number of seroconversions observed with each test virus strain. Convalescent phase sera that reacted with multiple virus strains often varied significantly in antibody titre from one virus strain to another. This indicates that, in some instances, antibody was probably produced in response to infection by different antigenic variants of CTF virus.


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