Infection of Mice, Ferrets, and Rhesus Macaques with a Clinical Mumps Virus Isolate

Abstract

e In recent years, many mumps outbreaks have occurred in vaccinated populations worldwide. The reasons for these outbreaks are not clear. Animal models are needed to investigate the causes of outbreaks and to understand the pathogenesis of mumps virus (MuV). In this study, we have examined the infection of three animal models with an isolate of mumps virus from a recent outbreak (MuV-IA). We have found that while both ferrets and mice generated humoral and cellular immune responses to MuV-IA infection, no obvious signs of illness were observed in these animals; rhesus macaques were the most susceptible to MuV-IA infection. Infection of rhesus macaques via both intranasal and intratracheal routes with MuV-IA led to the typical clinical signs of mumps 2 weeks to 4 weeks postinfection. However, none of the infected macaques showed any fever or neurologic signs during the experimental period. Mumps viral antigen was detected in parotid glands by immunohistochemistry (IHC). Rhesus macaques represent the best animal model for the study of mumps virus pathogenesis.

Immunogenicity of Novel Mumps Vaccine Candidates Generated by Genetic Modification

“…Enzyme-linked immunosorbent assay (ELISA) was performed as previously described (40). Briefly, immulon 2 HB 96-well microtiter plates (ThermoLab Systems) were coated with MuV proteins at 2 g/ml and incubated at 4°C overnight.…”

Mumps virus pathogenesis: Insights and knowledge gaps

“…11,12 One study with marmosets shows that intravenous inoculation with a clinical mumps virus isolate induces meningitis, whereas another study in which rhesus macaques were infected via the natural route with a clinical mumps virus isolate shows that these animals develop parotitis but no fever or neurological symptoms. 10,12 Although these findings suggest that monkeys might be a candidate model for mumps virus pathogenesis studies, the costs and ethical considerations limit the applicability of this model for mumps.…”

“…Mice and ferrets do not develop clinical symptoms and are considered poor candidates for pathogenesis studies. 10 Much of our current understanding of mumps virus pathogenesis is based on hamster and monkey models, but the unnatural routes of inoculation and the inability to distinguish attenuated mumps virus strains from wild-type strains makes the relevance of these findings questionable. 11,12 One study with marmosets shows that intravenous inoculation with a clinical mumps virus isolate induces meningitis, whereas another study in which rhesus macaques were infected via the natural route with a clinical mumps virus isolate shows that these animals develop parotitis but no fever or neurological symptoms.…”

“…25 Furthermore, the degree and duration of parotitis may be related to the amount of virus replication in the parotid gland and the development of a vigorous immune response, as was shown after experimental infection of rhesus macaques. 10 Replicating mumps virus has been isolated from the testis and semen, which indicates that orchitis is the result of direct invasion of the testicular cells. 27,28 Mumps virus shedding in urine is caused by dissemination of mumps virus to the kidneys and is associated with abnormal renal function.…”

Ferret airway epithelial cell cultures support efficient replication of influenza B virus but not mumps virus

“…Ferrets have also been used successfully to study infection and pathogenesis of several other human, animal or zoonotic viruses including CDV, SARS, RSV and Nipah (Bossart et al, 2009;Coates & Chanock, 1962;Martina et al, 2003). However, direct nasal inoculation of ferrets with clinical isolates or with vaccine strains of measles or mumps virus (MuV) did not lead to virus replication or disease (Parker et al, 2013;Pillet et al, 2009;Xu et al, 2013).…”