and safe type-specific bedside tests would be useful in the event of potential variola infection.

Diagnostic strategies could be verified using mouse or subhuman primate models of orthopoxvirus infection. A recombinant vaccinia virus carrying all or part of a variola virus gene would be useful for a step in the validation, subject to the concerns expressed above with regard to detection strategies. Research with a vaccinia virus construct carrying a single variola gene would not be constrained by the need to work in BSL-4 facilities. Some parallel work with monkeypox virus diagnostics in monkey models would be desirable to validate ease of detection in the context of an analogous primate virus-host model.

Alternatives to Live Virus

The development of detection and diagnostic strategies would not require live variola virus per se, beyond the need for additional recombinant DNA stocks and sequencing. Much of the developmental in vitro research could be done with isolated recombinant variola virus DNA and recombinant produced protein. The requirement for virus for field epidemiological detection, for particle stability verification, and for diagnostic test validation in experimental models could be bypassed by using vaccinia virus as a representative of the orthopoxvirus family. A vaccinia virus recombinant containing all or part of the relevant variola virus DNA segment would be useful for the validation of tests in appropriate epidemiological or experimental animal infection model systems, although assessment of the authenticity of the recombinant as compared with live variola virus would be needed. Parallel work with monkeypox virus might add a small margin of additional validation.



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