The current pandemic coronavirus, severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2), was recently identified in patients with an acute respiratory syndrome, coronavirus disease 2019 (COVID-19). To compare its pathogenesis with that of previously emerging coronaviruses, we inoculated cynomolgus macaques with SARS-CoV-2 or Middle East respiratory syndrome (MERS)–CoV and compared the pathology and virology with historical reports of SARS-CoV infections. In SARS-CoV-2–infected macaques, virus was excreted from nose and throat in the absence of clinical signs and detected in type I and II pneumocytes in foci of diffuse alveolar damage and in ciliated epithelial cells of nasal, bronchial, and bronchiolar mucosae. In SARS-CoV infection, lung lesions were typically more severe, whereas they were milder in MERS-CoV infection, where virus was detected mainly in type II pneumocytes. These data show that SARS-CoV-2 causes COVID-19–like disease in macaques and provides a new model to test preventive and therapeutic strategies.

The swine-origin A(H1N1) influenza virus that has emerged in humans in early 2009 has raised concerns about pandemic developments. In a ferret pathogenesis and transmission model, the 2009 A(H1N1) influenza virus was found to be more pathogenic than a seasonal A(H1N1) virus, with more extensive virus replication occurring in the respiratory tract. Replication of seasonal A(H1N1) virus was confined to the nasal cavity of ferrets, but the 2009 A(H1N1) influenza virus also replicated in the trachea, bronchi, and bronchioles. Virus shedding was more abundant from the upper respiratory tract for 2009 A(H1N1) influenza virus as compared with seasonal virus, and transmission via aerosol or respiratory droplets was equally efficient. These data suggest that the 2009 A(H1N1) influenza virus has the ability to persist in the human population, potentially with more severe clinical consequences.

The emergence of viral respiratory pathogens with pandemic potential, such as severe acute respiratory syndrome coronavirus (SARS-CoV) and influenza A H5N1, urges the need for deciphering their pathogenesis to develop new intervention strategies. SARS-CoV infection causes acute lung injury (ALI) that may develop into life-threatening acute respiratory distress syndrome (ARDS) with advanced age correlating positively with adverse disease outcome. The molecular pathways, however, that cause virus-induced ALI/ARDS in aged individuals are ill-defined. Here, we show that SARS-CoV-infected aged macaques develop more severe pathology than young adult animals, even though viral replication levels are similar. Comprehensive genomic analyses indicate that aged macaques have a stronger host response to virus infection than young adult macaques, with an increase in differential expression of genes associated with inflammation, with NF-κB as central player, whereas expression of type I interferon (IFN)-β is reduced. Therapeutic treatment of SARS-CoV-infected aged macaques with type I IFN reduces pathology and diminishes pro-inflammatory gene expression, including interleukin-8 (IL-8) levels, without affecting virus replication in the lungs. Thus, ALI in SARS-CoV-infected aged macaques developed as a result of an exacerbated innate host response. The anti-inflammatory action of type I IFN reveals a potential intervention strategy for virus-induced ALI.

Coronaviruses in the Middle East Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe acute respiratory illness and kills about a third of people infected. The virus is common in dromedary camels, which can be a source of human infections. In a survey for MERSCoV in over 1300 Saudi Arabian camels, Sabir et al. found that dromedaries share three coronavirus species with humans. Diverse MERS lineages in camels have caused human infections, which suggests that transfer among host species occurs quite easily. Haagmans et al. made a MERS-CoV vaccine for use in camels, using poxvirus as a vehicle. The vaccine significantly reduced virus excretion, which should help reduce the potential for transmission to humans, and conferred cross-immunity to camelpox infections. Science , this issue p. 81 , p. 77

In 2012, a previously unknown human coronavirus (CoV), now named Middle East respiratory syndrome CoV (MERS-CoV), was isolated from the sputum of a 60-year-old man in Saudi Arabia who presented with acute pneumonia with a fatal outcome (1, 2). To date, several infection clusters have been reported over a 1-year period, with around 50% of the reported human cases being fatal (3). MERS-CoV represents a novel betacoronavirus species, with the closest known relatives being clade 2c bat CoVs detected in bats (4, 5). Although MERS-CoV replicates in cells of bats, pigs, and (non-)human primates (6), its ability to infect some animal species may be restricted given the fact that hamsters were shown to resist MERS-CoV infection (7). However, these host factors have not been well characterized.We recently identified dipeptidyl peptidase 4 (DPP4) as a functional MERS-CoV receptor in human and bat cells (8). To further analyze DPP4 usage by MERS-CoV in vivo, ferrets (Mustela putorius furo; n ϭ 4), known to be susceptible to several respiratory viruses, including severe acute respiratory syndrome CoV (SARS- staining or S1-Fc binding on ferret kidney cells incubated with either goat anti-DPP4 polyclonal serum or S1-Fc (5 g/ml) followed by incubation with fluorescein isothiocyanate (FITC)-labeled rabbit anti-goat IgG antibody or FITC-labeled goat anti-human IgG, respectively (red lines). Normal goat serum, feline CoV S1-Fc protein (blue lines), and mock-incubated cells (gray shading) were used as controls. (E) MERS-CoV infection of primary ferret kidney cells transfected with a control plasmid or with a plasmid encoding hDPP4, stained for DPP4, S1 binding, and MERS-CoV as described previously (13).