Hooi, Yuan Teng and Ong, Kien Chai and Tan, Soon Hao and Perera, David and Wong, Kum Thong (2020) A novel orally infected hamster model for Coxsackievirus A16 hand-foot-and-mouth disease and encephalomyelitis. Laboratory Investigation, 100 (9). pp. 1262-1275. ISSN 00236837, DOI https://doi.org/10.1038/s41374-020-0456-x.
Full text not available from this repository.Abstract
Coxsackievirus A16 (CV-A16) is one of the major causes of mild and self-limiting hand-foot-and-mouth disease (HFMD) in young children, which may occasionally leads to serious neurological complications. In this study, we had developed a novel, consistent, orally infected CV-A16 HFMD hamster model with encephalomyelitis. Four groups of 7-day-old hamsters in a kinetic study were orally infected with mouse-adapted CV-A16 strains and sacrificed at 1-4 days post infection (dpi), respectively. Tissues were studied by light microscopy, immunohistochemistry to detect viral antigens, in situ hybridization to detect viral RNA, and by viral titration. In a separate transmission experiment, orally infected index hamsters were housed together with contact hamsters to investigate oral and fecal viral shedding by virus culture and reverse transcription polymerase chain reaction (RT-PCR). At severe infection/death endpoints, index and contact hamster infection were also histopathologically analyzed. In the kinetic study, infected hamsters developed signs of infection at 4 dpi. Viral antigens/RNA were localized to brainstem (medulla/pons; reticular formation and motor trigeminal nucleus) and spinal cord anterior horn neurons, oral squamous epithelia and epidermis from 3 to 4 dpi. Salivary and lacrimal glands, myocardium, brown adipose tissue, intestinal smooth muscle, and skeletal muscle infection was also demonstrated. Viremia at 1 dpi and increasing viral titers in various tissues were observed from 2 dpi. In the transmission study, all contact hamsters developed disease 3-5 days later than index hamsters, but demonstrated similar histopathological findings at endpoint. Viral culture and RT-PCR positive oral washes and feces confirmed viral shedding. Our hamster model, orally infected by the natural route for human infection, confirmed CV-A16 neurotropism and demonstrated squamous epitheliotropism reminiscent of HFMD, attributes not found in other animal models. It should be useful to investigate neuropathogenesis, model person-to-person transmission, and for testing antiviral drugs and vaccines. An orally infected hamster model of Coxsackievirus A16 (CV-A16) hand-foot-and-mouth disease (HFMD) and encephalomyelitis demonstrating central nervous system and squamous epithelial infection, reminiscent of complicated human CV-A16 HFMD is described. This novel and consistent animal model should be useful to investigate viral pathogenesis, model person-to-person transmission, and to test antivirals and vaccines.
| Item Type: | Article |
|---|---|
| Funders: | UNSPECIFIED |
| Uncontrolled Keywords: | Animals; Antigens, Viral; Child; Cricetinae; Disease Models, Animal; Encephalomyelitis; Enterovirus A |
| Subjects: | R Medicine > R Medicine (General) R Medicine > RB Pathology |
| Divisions: | Faculty of Medicine Faculty of Medicine > Biomedical Science Department Faculty of Medicine > Pathology Department |
| Depositing User: | Ms Zaharah Ramly |
| Date Deposited: | 28 Jun 2024 03:02 |
| Last Modified: | 28 Jun 2024 03:02 |
| URI: | http://eprints.um.edu.my/id/eprint/36599 |
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