Vaccine and antiviral development against SARS-CoV-2 infection or COVID-19 disease would benefit from validated small animal models. Here, we show that transgenic mice expressing human angiotensin-converting enzyme 2 (hACE2) by the human cytokeratin 18 promoter (K18 hACE2) represent a susceptible rodent model. K18 hACE2 transgenic mice succumbed to SARS-CoV-2 infection by day 6, with virus detected in lung airway epithelium and brain. K18 ACE2 transgenic mice produced a modest TH1/2/17 cytokine storm in the lung and spleen that peaked by day 2, and an extended chemokine storm that was detected in both lungs and brain. This chemokine storm was also detected in the brain at day 6. K18 hACE2 transgenic mice are, therefore, highly susceptible to SARS-CoV-2 infection and represent a suitable animal model for the study of viral pathogenesis, and for identification and characterization of vaccines (prophylactic) and antivirals (therapeutics) for SARS-CoV-2 infection and associated severe COVID-19 disease.

During its most recent outbreak across the Americas, Zika virus (ZIKV) was surprisingly shown to cause fetal loss and congenital malformations in acutely and chronically infected pregnant women. However, understanding the underlying pathogenesis of ZIKV congenital disease has been hampered by a lack of relevant in vivo experimental models. Here we present a candidate New World monkey model of ZIKV infection in pregnant marmosets that faithfully recapitulates human disease. ZIKV inoculation at the human-equivalent of early gestation caused an asymptomatic seroconversion, induction of type I/II interferon-associated genes and proinflammatory cytokines, and persistent viremia and viruria. Spontaneous pregnancy loss was observed 16–18 days post-infection, with extensive active placental viral replication and fetal neurocellular disorganization similar to that seen in humans. These findings underscore the key role of the placenta as a conduit for fetal infection, and demonstrate the utility of marmosets as a highly relevant model for studying congenital ZIKV disease and pregnancy loss.

Adenoviruses (AdVs) are DNA viruses that infect many vertebrate hosts, including humans and nonhuman primates. Here we identify a novel AdV species, provisionally named “simian adenovirus C (SAdV-C),” associated with a 1997 outbreak of acute respiratory illness in captive baboons (4 of 9) at a primate research facility in Texas. None of the six AdVs recovered from baboons (BaAdVs) during the outbreak, including the two baboons who died from pneumonia, were typeable. Since clinical samples from the two fatal cases were not available, whole-genome sequencing of nasal isolates from one sick baboon and three asymptomatic baboons during the outbreak was performed. Three AdVs were members of species SAdV-C (BaAdV-2 and BaAdV-4 were genetically identical, and BaAdV-3), while one (BaAdV-1) was a member of the recently described SAdV-B species. BaAdV-3 was the only AdV among the 4 isolated from a sick baboon, and thus was deemed to be the cause of the outbreak. Significant divergence (<58% amino acid identity) was found in one of the fiber proteins of BaAdV-3 relative to BaAdV-2 and -4, suggesting that BaAdV-3 may be a rare SAdV-C recombinant. Neutralizing antibodies to the other 3 AdVs, but not BaAdV-3, were detected in healthy baboons from 1996 to 2003 and staff personnel from 1997. These results implicate a novel adenovirus species (SAdV-C) in an acute respiratory outbreak in a baboon colony and underscore the potential for cross-species transmission of AdVs between humans and nonhuman primates. IMPORTANCE Adenoviruses (AdVs) are DNA viruses that infect many animals, including humans and monkeys. In 1997, an outbreak of acute respiratory illness from AdVs occurred in a baboon colony in Texas. Here we use whole-genome sequencing and antibody testing to investigate new AdVs in baboons (BaAdVs) during the outbreak, one of which, BaAdV-3, came from a sick animal. By sequence analysis, BaAdV-3 may be a recombinant strain that arose from a related BaAdV found in baboons nearby in the colony (who were not sick) and yet another unknown AdV. We also found antibodies to these new BaAdVs in baboons and staff personnel at the facility. Taken together, our findings of a new AdV species as the cause of an acute respiratory outbreak in a baboon colony underscore the ongoing threat from emerging viruses that may carry the potential for cross-species transmission between monkeys and humans.