Severity of enterovirus A71 infection in a human SCARB2 knock-in mouse model is dependent on infectious strain and route.

Enterovirus A71 (EV-A71) is a major etiological agent of human hand, foot and mouth disease, and it can cause severe neurological complications. Although several genotypes of EV-A71 strains are prevalent in different regions of the world, the genotype C4 has circulated in mainland China for more than 20 years. The pathogenicity of different EV-A71 clinical isolates varies and needs to be explored. In this study, hSCARB2 knock-in mice (N = 181) with a wide range of ages were tested for their susceptibility to two EV-A71 strains with the subgenotypes C4 and C2, and two infection routes (intracranial and venous) were compared. The clinical manifestations and pathology and their relationship to the measured viral loads in different tissues were monitored. We observed that 3 weeks is a crucial age, as mice younger than 3-week-old that were infected became extremely ill. However, mice older than 3 weeks displayed diverse clinical symptoms. Significant differences were observed in the pathogenicity of the two strains with respect to clinical signs, disease incidence, survival rate, and body weight change. We concluded that hSCARB2 knock-in mice are a sensitive model for investigating the clinical outcomes resulting from infection by different EV-A71 strains. The intracranial infection model appears to be suitable for evaluating EV-A71 neurovirulence, whereas the venous infection model is appropriate for studying the pathogenicity of EV-A71.

Effects of mammarenavirus infection (Wenzhou virus) on the morphology of Rattus exulans.

The circulation of mammarenaviruses in rodent populations of the Mekong region has recently been established, with a genetic variant of Wenzhou virus, Cardamones virus, detected in two Rattus species. This study tests the potential teratogenic effects of Wenzhou infection on the development of a Murid rodent, Rattus exulans. Using direct virus detection, morphological records and comparative analyses, a link was demonstrated between host infection status and host morphologies (the spleen irrespective of weight, the skull shape and the cranial cavity volume) at the level of the individual (females only). This study demonstrates that mammarenavirus infections can impact natural host physiology and/or affect developmental processes. The presence of an infecting micro-parasite during the development of the rat may lead to a physiological trade-off between immunity and brain size. Alternatively, replication of virus in specialized organs can result in selective morphologic abnormalities and lesions.

Detection of retroviruses in a calvaria of a young mouse.

During systematic examination of the development and growth of mouse calvariae, virus particles were detected electron microscopically. Mice, strain NMRI, were obtained from the breeder Harlan-Winkelmann (Borchem, Germany) and mated in the animal house. The area of the sagittal suture from day-18 foetuses and from different stages until day-26 pp as well as from adult mice was studied. In the calvaria of a day-21 pp mouse, type-C virus particles were found in the pericellular space of many, but not all osteogenic cells. The morphology of all viruses found resembled that of retroviruses; they were regular in size, spherical and showed a diameter of 100-120 nm. Budding of viruses from the osteocyte membrane occurred frequently. Also type-A particles were detected intracisternally within the rough endoplasmic reticulum. Budding of type-C virus particles, extracellular deposition of retroviruses and intracisternal formation of type-A particles occurred in the same cell. However, although examinations of 22 different individual calvariae were done, only one obtained from a day-21 pp mice was virus-positive. Most probably, this observation is due to an endogenous virus production. Several mouse strains bear provirus DNA in their genome; the mode of activation of which is unknown. Reports in the literature are rare. Nevertheless, virus-infected material may influence experimental approaches and may be dangerous for the people who work with such material.