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clade I virus escaping from Africa in the future. A goal of my mpox research is to determine the basis for the greater virulence of clade I compared to clade II viruses to better contain such a potential outbreak. A step toward this goal has keen the development of a small animal model that mimics the severity of human disease caused by clade I and clade II mpox viruses. The work was published this year showing that the lethality of mpox virus in our model is clade I > clade IIa > clade IIb. The finding that the current clade IIb outbreak strain is less virulent than either clade I or clade IIa in our model is consistent with the self-limiting disease in immunocompetent adults, although mpox can be devastating in individuals with AIDS or other immunodeficiencies.
Our next step is to use this model to determine the basis for the differences in virulence of mpox virus clades I and II. Fortunately, we developed the tools to do this during our previous research. The virulence genes of vaccinia virus, the vaccine used to prevent smallpox, were identified by constructing recombinant viruses in which genes were deleted or modified and testing them in animal models. We received approval from the Institutional Biosafety Committee to carry out related experiments in which genes from the more virulent mpox clade I virus were replaced with the corresponding genes from the less virulent clade IIa virus. The expectation of such experiments is that chimeric clade I virus will be attenuated when the genes responsible for virulence are replaced. However, mpox virus contains about 200 genes, so this is an arduous task and is still ongoing. Depending on the results of these experiments, I will consider additional gene exchanges that might include transfers in the opposite direction or involve clade IIb. I have not planned or proposed such experiments for approval since we have not completed the current experiments and therefore do not yet know which genes might be best to transfer. However, should it appear in the future that such an experiment would greatly contribute to understanding the basis for mpox virus virulence, then I may make such a proposal and would abide by the decision of the Institutional Biosafety Committee.
Lastly, with respect to the Science magazine article referenced in your letter, it would have been more accurate for that reporter to use the word “considering” rather than “planning” to represent the stage of my thinking about potential future research on the mpox virus.
Sincerely yours,
A personal signature appears here
Bernard Moss M.D., Ph.D.
NIH Distinguished Investigator
Laboratory of Viral Diseases, NIAID
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