At the end of 2019, a novel coronavirus (severe acute respiratory syndrome coronavirus 2; SARS-CoV-2) was detected in Wuhan, China, that spread rapidly around the world, with severe consequences for human health and the global economy. Here, we assessed the replicative ability and pathogenesis of SARS-CoV-2 isolates in Syrian hamsters. SARS-CoV-2 isolates replicated efficiently in the lungs of hamsters, causing severe pathological lung lesions following intranasal infection. In addition, microcomputed tomographic imaging revealed severe lung injury that shared characteristics with SARS-CoV-2−infected human lung, including severe, bilateral, peripherally distributed, multilobular ground glass opacity, and regions of lung consolidation. SARS-CoV-2−infected hamsters mounted neutralizing antibody responses and were protected against subsequent rechallenge with SARS-CoV-2. Moreover, passive transfer of convalescent serum to naïve hamsters efficiently suppressed the replication of the virus in the lungs even when the serum was administrated 2 d postinfection of the serum-treated hamsters. Collectively, these findings demonstrate that this Syrian hamster model will be useful for understanding SARS-CoV-2 pathogenesis and testing vaccines and antiviral drugs.

Marburg virus (MARV), a member of the filovirus family, causes severe hemorrhagic fever with up to 90% lethality. MARV matrix protein VP40 is essential for assembly and release of newly copied viruses and also suppresses immune signaling in the infected cell. Here we report the crystal structure of MARV VP40. We found that MARV VP40 forms a dimer in solution, mediated by N-terminal domains, and that formation of this dimer is essential for budding of virus-like particles. We also found the N-terminal domain to be necessary and sufficient for immune antagonism. The C-terminal domains of MARV VP40 are dispensable for immunosuppression but are required for virus assembly. The C-terminal domains are only 16% identical to those of Ebola virus, differ in structure from those of Ebola virus, and form a distinct broad and flat cationic surface that likely interacts with the cell membrane during virus assembly. IMPORTANCEMarburg virus, a cousin of Ebola virus, causes severe hemorrhagic fever, with up to 90% lethality seen in recent outbreaks. Molecular structures and visual images of the proteins of Marburg virus are essential for the development of antiviral drugs. One key protein in the Marburg virus life cycle is VP40, which both assembles the virus and suppresses the immune system. Here we provide the molecular structure of Marburg virus VP40, illustrate differences from VP40 of Ebola virus, and reveal surfaces by which Marburg VP40 assembles progeny and suppresses immune function. Marburg virus (MARV) and the related Ebola virus (EBOV) both belong to the Filoviridae family. These are enveloped viruses with a nonsegmented single-stranded and negative-sense RNA genome. Genomes of Marburg viruses differ from those of ebolaviruses by more than 50% at the nucleotide level (1). MARV causes severe and rapidly progressing hemorrhagic fever in humans and nonhuman primates, with lethality ranging from 25% to over 90% depending on the geographic location and viral strain (2). The 19-kb MARV genome encodes seven structural proteins. Each of these proteins is of critical importance, and most are known to perform multiple functions during the viral life cycle.VP40 is the Marburg virus matrix protein, which builds the protein shell underneath the viral envelope and confers the hallmark filamentous morphology to the Marburg virion. VP40 alone is able to induce the assembly and budding of filamentous viruslike particles (VLPs), which resemble authentic virions (3, 4). The intracellular distribution of filovirus VP40 varies during the progression of the viral life cycle (5, 6), as it orchestrates the distribution of the other viral components and viral assembly (6, 7). The majority of it, however, traffics to and associates with the cellular membrane (5,7,8). Within the virion, VP40 interacts with both the lipid envelope and the core nucleocapsid complex, which contains the NP, VP35, L, VP30, and VP24 proteins (9). VP40 also interacts with the GP viral surface protein. Indeed, coexpression of VP40 and GP alters the distributi...

The search for potential antibody-based diagnostics, vaccines, and therapeutics for pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has focused almost exclusively on the spike (S) and nucleocapsid (N) proteins. Coronavirus membrane (M), ORF3a, and ORF8 proteins are humoral immunogens in other coronaviruses (CoVs) but remain largely uninvestigated for SARS-CoV-2. Here, we use ultradense peptide microarray mapping to show that SARS-CoV-2 infection induces robust antibody responses to epitopes throughout the SARS-CoV-2 proteome, particularly in M, in which 1 epitope achieved excellent diagnostic accuracy. We map 79 B cell epitopes throughout the SARS-CoV-2 proteome and demonstrate that antibodies that develop in response to SARS-CoV-2 infection bind homologous peptide sequences in the 6 other known human CoVs. We also confirm reactivity against 4 of our top-ranking epitopes by enzyme-linked immunosorbent assay (ELISA). Illness severity correlated with increased reactivity to 9 SARS-CoV-2 epitopes in S, M, N, and ORF3a in our population. Our results demonstrate previously unknown, highly reactive B cell epitopes throughout the full proteome of SARS-CoV-2 and other CoV proteins.

We thank Erik Boehm for editorial assistance. We thank Gert Zimmer for the donation of vesicular stomatitis virus recombinant, Jay W. Hooper from the United States Army Medical Research Institute of Infectious Diseases for the plasmid encoding Puumala glycoprotein, and Jennifer Mayor for the production of recombinant vesicular stomatitis virus with Puumala virus glycoprotein. We are deeply grateful to the family for their permission to publish this article.

Viruses infect cells mainly via specific receptors at the cell surface. Antibody-dependent enhancement (ADE) of infection is an alternative mechanism of infection for viruses to infect immune cells that is mediated by antibodies and IgG receptors (FcγRs).