Clinical Course and Pathology in Rats (Rattus norvegicus) After Experimental Cowpox Virus Infection by Percutaneous and Intranasal Application

Abstract

Recently, several cases of human cowpox virus (CPXV) infections were reported in France and Germany, which had been acquired through close contact with infected pet rats. The animals exhibited respiratory signs or skin lesions and died shortly after purchase. After natural infection of white rats with CPXV in the USSR in 1978, a peracute pulmonary form, a milder dermal form, and a mixed form exhibiting features of both have been described. To the best of the authors' knowledge, 3 experimental cowpox virus infection studies using rats have been performed to date; however, neither results of histomorphological examinations nor immunohistochemical analyses have yet been reported in rats after experimental infections. To investigate the impact of the infection route on the clinical course, the development of lesions, and tropism, rats were infected intradermally, intranasally, or by a combination of both routes. The authors found a correlation between clinical manifestation, pathology, and infection routes. Intradermal and contact exposure yielded a mild dermal form, characterized by the development of vesiculopustular dermatitis. In contrast, intranasally infected animals died peracutely, showing severe dyspnea. Occasionally, a combination of the dermal and the respiratory form occurred after intranasal infection. Immunohistochemically, CPXV antigen was detected in the epithelial and mesenchymal cells of the upper respiratory tract and affected skin lesions and rarely in mesenchymal cells of lymph nodes. This is the first histomorphological and immunohistochemical analysis of CPXV in rats after experimental infection.

Out of the Reservoir: Phenotypic and Genotypic Characterization of a Novel Cowpox Virus Isolated from a Common Vole

“…The experimental design complied with the experiments published previously (17,18). Eleven rats and 9 common voles were infected oronasally with CPXV strain FM2292 in two groups using titers of 10 4 and 10…”

“…Indeed, the only reported vole reservoir sample from which CPXV was isolated originated from a Russian root vole (15), but that virus was never characterized in any detail. In addition, whereas laboratory breeds of selected mouse strains are used for CPXV inhibitor research (16) and whereas rats are used for assessment of viral pathogenicity (17,18), the nature of CPXV infection in common voles has never been documented.…”

Emergence of Cowpox: Study of the Virulence of Clinical Strains and Evaluation of Antivirals

“…The role of IL-6 induction in cowpox pathogenesis remains still unclear but a recent article evidenced that IL-6, IL-8 and CXCL1, produced upon in vitro CPXV-BR infection, could be responsible for chemotaxis of monocytes in vitro [23]. Additionally, macrophages and monocytes are suspected to be involved in CPXV spread through the host [30]. A potential role of IL-6 in CPXV pathogenesis might also be supported by the fact that, during inflammation, IL-6 has been shown to suppress neutrophils recruitment at sites of acute inflammation, making ways for the influx of monocytes as the inflammatory response is sustained [21].…”

Viral Disease

“…Rats inoculated with cowpox were reported to have proliferative and necrotizing dermatitis and folliculitis, ulcerativeenecrotizing rhinitis and pharyngitis, bronchointerstitial pneumonia, pulmonary edema, and emphysema. Contact sentinel rats had dermal lesions but did not develop upper or lower respiratory lesions (Breithaupt et al, 2012). Histologically, all poxviruses produce basophilic intracytoplasmic inclusions (type B, or Guarnieri bodies) in infected epithelial cells, while CPXV and ectromelia virus also produce eosinophilic/ acidophilic intracytoplasmic inclusions (type A).…”

“…Experimental infection of 4-to 6-week-old Wistar rats with CPXV resulted in clinical symptoms and dermal lesions in 6e11 days; rats had detectable virus in oropharyngeal secretions on day 5 and the majority of rats had detectable viral DNA in the nose, lung, esophagus, liver, spleen, skin, and brain on day 10 (Kalthoff et al, 2011). Severity of disease is related to the route of infection.Intranasal or combined intranasal/intradermal inoculation resulted in severe disease, and rats died peracutely with severe dyspnea and lethargy, whereas rats inoculated intradermally or infected by exposure to CPXV-infected rats had less severe disease characterized primarily by dermal lesions and survived until the end of the experiment (11 or 36 days) (Breithaupt et al, 2012). Rats inoculated with cowpox were reported to have proliferative and necrotizing dermatitis and folliculitis, ulcerativeenecrotizing rhinitis and pharyngitis, bronchointerstitial pneumonia, pulmonary edema, and emphysema.…”