RESUMO
COVID-19, caused by SARS-CoV-2 infection, has recently been announced as a pandemic all over the world. Plenty of diagnostic, preventive and therapeutic knowledges have been enriched from clinical studies since December 2019. However, animal models, particularly non-human primate models, are urgently needed for critical questions that could not be answered in clinical patients, evaluations of anti-viral drugs and vaccines. In this study, two families of non-human primates, Old world monkeys (12 Macaca mulatta, 6 Macaca fascicularis) and New world monkeys (6 Callithrix jacchus), were experimentally inoculated with SARS-CoV-2. Clinical signs were recorded. Samples were collected for analysis of viral shedding, viremia and histopathological examination. Increased body temperature was observed in 100% (12/12) M. mulatta, 33.3% (2/6) M. fascicularis and none (0/6) of C. jacchus post inoculation of SARS-CoV-2. All of M. mulatta and M. fascicularis showed chest radiographic abnormality. Viral genomes were detected in nasal swabs, throat swabs, anal swabs and blood from all 3 species of monkeys. Viral shedding from upper respiratory samples reached the peak between day 6 and day 8 post inoculation. From necropsied M. mulatta and M. fascicularis, the tissues showing virus positive were mainly lung, weasand, bronchus and spleen. No viral genome was seen in any of tissues from 2 necropsied C. jacchus. Severe gross lesions and histopathological changes were observed in lung, heart and stomach of SARS-CoV-2 infected animals. In summary, we have established a NHP model for COVID-19, which could be used to evaluate drugs and vaccines, and investigate viral pathogenesis. M. mulatta is the most susceptible to SARS-CoV-2 infection, followed by M. fascicularis and C. jacchus. One Sentence SummaryM. mulatta is the most susceptible to SARS-CoV-2 infection as compared to M. fascicularis and C. jacchus.
RESUMO
Hand, foot and mouth disease (HFMD) has been prevalent in China since 2008. Enterovirus 71 (EV71) is a common causative agent of HFMD, and various strains of EV71 are prevalent worldwide. The EV71C4 subgenotype is the most endemic strain in China. However, few studies investigating the biological characteristics and pathogeneses of different C4 strains have been reported. Therefore, the current study investigated 19 clinical EV71 strains in neonatal ICR mice and neonatal rhesus monkeys by comparing pathogenicity; the virulence of different viral passages, dosages, and routes of infection; and the effects produced by subject animal age. These 19 clinical EV71 strains, which were of the same subtype, displayed varying pathogenic effects. Three strains (HE31, 231 and 262) induced limb paralysis in neonatal ICR mice. In addition, the degree of virulence was largely dependent upon the dose, route of infection, and number of passages of the challenge virus, as well as the ages of the infected animals. The present study provides valuable basic data to enable further research into EV71 pathogenesis and to facilitate the development of new drugs and vaccines.
