Date Published: January 27, 2010
Publisher: Public Library of Science
Author(s): Christina L. Hutson, Jason A. Abel, Darin S. Carroll, Victoria A. Olson, Zachary H. Braden, Christine M. Hughes, Michael Dillon, Consuelo Hopkins, Kevin L. Karem, Inger K. Damon, Jorge E. Osorio, Wanda Markotter. http://doi.org/10.1371/journal.pone.0008912
Abstract: Although monkeypox virus (MPXV) studies in wild rodents and non-human primates have generated important knowledge regarding MPXV pathogenesis and inferences about disease transmission, it might be easier to dissect the importance of virulence factors and correlates of protection to MPXV in an inbred mouse model. Herein, we compared the two clades of MPXV via two routes of infection in the BALB/c and C57BL/6 inbred mice strains. Our studies show that similar to previous animal studies, the Congo Basin strain of MPXV was more virulent than West African MPXV in both mouse strains as evidenced by clinical signs. Although animals did not develop lesions as seen in human MPX infections, localized signs were apparent with the foot pad route of inoculation, primarily in the form of edema at the site of inoculation; while the Congo Basin intranasal route of infection led to generalized symptoms, primarily weight loss. We have determined that future studies with MPXV and laboratory mice would be very beneficial in understanding the pathogenesis of MPXV, in particular if used in in vivo imaging studies. Although this mouse model may not suffice as a model of human MPX disease, with an appropriate inbred mouse model, we can unravel many unknown aspects of MPX pathogenesis, including virulence factors, disease progression in rodent hosts, and viral shedding from infected animals. In addition, such a model can be utilized to test antivirals and the next generation of orthopoxvirus vaccines for their ability to alter the course of disease.
Partial Text: Human monkeypox (MPX) is a sporadic smallpox-like zoonotic viral exanthemata disease that occurs in the rain forests of Central and West Africa. The virus was discovered in 1958 from primate tissues. The disease has similar manifestations to those of smallpox but tends to be less severe. The virus MPX belongs to the Orthopoxvirus genus of Poxviridae, and shares many biochemical and physical properties with other orthopoxviruses, such as vaccinia and variola (causative agent of smallpox). MPXV is endemic in the rain forests of Central and West Africa, causing sporadic outbreaks in remote villages, where it is believed to result from close contact between humans and animals living in the rain forests–. MPXV infection is thought to be acquired most commonly by direct percutaneous contact, mucosal or respiratory exposure to tissues or fluids of infected animals.
In the present study, we compared the infection produced by West African and Congo Basin MPXV clades in inbred BALB/c and C57BL/6 mice. Subtle differences in pathogenicity between the two strains of MPXV were observed in this study. As seen in previous animal studies, , the Congo Basin strain of MPXV was more virulent than the West African strain as evidenced by the symptoms we observed. We have determined that laboratory mice may be a suitable animal model to study MPXV pathogenesis and future studies to further characterize the mouse innate and adaptive immune responses to monkeypox infection will help in understanding the host-virus interactions that lead to more attenuated disease presentations compared to people and other animals such as prairie dogs.