The pathogenicity of the various MPOV virus clades differs significantly, according to a new mouse model

 

By Emily Henderson

February 14, 2023

A significant barrier to a better understanding of mpox has been removed by researchers from the National Institute of Allergy and Infectious Diseases (NIAID), a division of the National Institutes of Health (formerly, monkeypox). They created a mouse illness model and utilised it to show how the main genetic subgroups (clades) of the MPXV virus differed significantly in terms of virulence. Bernard Moss, M.D., Ph.D., head of the Genetic Engineering Section of NIAID's Laboratory of Viral Diseases, led the study, which was published in Proceedings of the National Academy of Science.

Historically, rodents rarely transmitted the disease known as mpox, which is similar to smallpox, to non-human primates or humans. This disease was mostly seen in several African nations. Rarely does MPOX spread from one individual to another. With an outbreak in 2022 that saw person-to-person MPOX transmission in more than 100 locations worldwide, this trend was disrupted. Over 80,000 measles cases have been identified so far in this outbreak. The strain causing the present epidemic, clade IIb, was identified through genome sequencing as being distinct from two previous clades, clade I, which has a mortality rate of up to 10%, and clade IIa, which has a mortality rate of less than 1%. Clade IIb MPXV has a lower mortality rate than any of the historical clades.

Standard inbred laboratory mice are immune to MPXV infection, and it is challenging to investigate how genetic variations contribute to observed variations in virulence due to the lack of a small animal model of MPX. Dr. Moss and his associates discovered a strain of inbred, wild-derived lab mice known as CAST/EiJ and found that MPXV may infect these animals. In CAST mice, clade I was the most virulent, then clade IIa, and subsequently clade IIb. Unexpectedly, clade IIb virus in mice was 100 times less virulent than clade IIa virus and caused significantly less viral replication than either of the previous clades. 

Despite being exposed to exceptionally high viral dosages, no mice perished from Clade IIb infection. The researchers draw the conclusion that the data taken together point to Clade IIb evolving less virulence or adapting to other species.