Intranasal infection of hSCARB2-transgenic mice with Coxsackievirus A16 resulted in productive infection with clear tropism to lung and brain tissues, causing weight loss and interstitial pneumonia.
Does intranasal infection with CA16 in hSCARB2-transgenic mice model the respiratory and neurological pathogenesis of human HFMD?
hSCARB2-transgenic mice infected intranasally with CA16 serve as a viable model for studying the respiratory and neurological pathogenesis of hand, foot, and mouth disease.
BACKGROUND: Coxsackievirus A16 (CA16) is one of the neurotropic pathogen that has been associated with severe neurological forms of hand, foot, and mouth disease (HFMD), but its pathogenesis is not yet clear. The limited host range of CA16 make the establishment of a suitable animal model that can recapitulate the neurological pathology observed in human HFMD more difficult. Because the human scavenger receptor class B, member 2 (hSCARB2) is a cellular receptor for CA16, we used transgenic mice bearing human SCARB2 and nasally infected them with CA16 to study the pathogenicity of the virus. METHODS: Coxsackievirus A16 was administered by intranasal instillation to groups of hSCARB2 transgenic mice and clinical signs were observed. Sampled at different time-points to document and characterize the mode of viral dissemination, pathological change and immune response of CA16 infection. RESULTS: Weight loss and virus replication in lung and brain were observed in hSCARB2 mice infected with CA16, indicating that these animals could model the neural infection process. Viral antigens were observed in the alveolar epithelia and brainstem cells. The typical histopathology was interstitial pneumonia with infiltration of significant lymphocytes into the alveolar interstitial in lung and diffuse punctate hemorrhages in the capillaries of the brainstem. In addition, we detected the expression levels of inflammatory cytokines and detected high levels of interleukin IL-1β, IL-6, IL-18, and IFN-γ in nasal mucosa, lungs and brain tissues. CONCLUSIONS: The hSCARB2-transgenic mice can be productively infected with CA16 via respiratory route and exhibited a clear tropism to lung and brain tissues, which can serve as a model to investigate the pathogenesis of CA16 associated respiratory and neurological disease.
Chen et al. (Wed,) conducted a other in Coxsackievirus A16 infection (n=35). Coxsackievirus A16 (CA16) intranasal infection vs. Mock infection (PBS) and wild-type mice was evaluated on Clinical signs (weight loss, survival), viral dissemination, and pathological changes. Intranasal infection of hSCARB2-transgenic mice with Coxsackievirus A16 resulted in productive infection with clear tropism to lung and brain tissues, causing weight loss and interstitial pneumonia.