Laboratory Investigations of African Pouched Rats ( Cricetomys gambianus) as a Potential Reservoir Host Species for Monkeypox Virus

Abstract

Monkeypox is a zoonotic disease endemic to central and western Africa, where it is a major public health concern. Although Monkeypox virus (MPXV) and monkeypox disease in humans have been well characterized, little is known about its natural history, or its maintenance in animal populations of sylvatic reservoir(s). In 2003, several species of rodents imported from Ghana were involved in a monkeypox outbreak in the United States with individuals of three African rodent genera ( Cricetomys, Graphiurus, Funisciurus) shown to be infected with MPXV. Here, we examine the course of MPXV infection in Cricetomys gambianus (pouched Gambian rats) and this rodent species’ competence as a host for the virus. We obtained ten Gambian rats from an introduced colony in Grassy Key, Florida and infected eight of these via scarification with a challenge dose of 4X10 ⁴ plaque forming units (pfu) from either of the two primary clades of MPXV: Congo Basin (C-MPXV: n = 4) or West African (W-MPXV: n = 4); an additional 2 animals served as PBS controls. Viral shedding and the effect of infection on activity and physiological aspects of the animals were measured. MPXV challenged animals had significantly higher core body temperatures, reduced activity and increased weight loss than PBS controls. Viable virus was found in samples taken from animals in both experimental groups (C-MPXV and W-MPXV) between 3 and 27 days post infection (p.i.) (up to 1X10 ⁸ pfu/ml), with viral DNA found until day 56 p.i. The results from this work show that Cricetomys gambianus (and by inference, probably the closely related species, Cricetomys emini) can be infected with MPXV and shed viable virus particles; thus suggesting that these animals may be involved in the maintenance of MPXV in wildlife mammalian populations. More research is needed to elucidate the epidemiology of MPXV and the role of Gambian rats and other species.

Author Summary

Post smallpox eradication, Monkeypox virus (MPXV) has emerged as the most important human health threat within the Orthopoxvirus genus. Sporadic outbreaks of monkeypox within Africa, concern over the potential of the virus to move outside of its natural range, as well as the increasing proportion of unvaccinated people now susceptible to MPXV (due to cessation of smallpox vaccination), makes it important to understand how the virus is transmitted to humans within Africa. Thus far the natural reservoir(s) of MXPV has eluded identification; however several rodent species including African pouched rats ( Cricetomys spp.) have been implicated as possible reservoirs. Cricetomys are often found living in close proximity to humans (and invading homes) and additionally serve as a food source within Africa. Therefore, it is important to utilize laboratory methods to examine the course of MPXV infection in Cricetomys and thus determine this rodent species’ competence as a host for the virus. We challenged eight animals with MPXV (4X10 ⁴ pfu) and assessed clinical symptoms and molecular markers of disease. Our results show Cricetomys can be infected with MPXV and shed high loads of virus via multiple routes, supporting the hypothesis that they may be involved in the maintenance and transmission of the virus within Africa.