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The global emergence of many severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants jeopardizes the protective antiviral immunity induced after infection or vaccination. To address the public health threat caused by the increasing SARS-CoV-2 genomic diversity, the National Institute of Allergy and Infectious Diseases within the National Institutes of Health established the SARS-CoV-2 Assessment of Viral Evolution (SAVE) programme. This effort was designed to provide a real-time risk assessment of SARS-CoV-2 variants that could potentially affect the transmission, virulence, and resistance to infection- and vaccine-induced immunity. The SAVE programme is a critical data-generating component of the US Government SARS-CoV-2 Interagency Group to assess implications of SARS-CoV-2 variants on diagnostics, vaccines and therapeutics, and for communicating public health risk. Here we describe the coordinated approach used to identify and curate data about emerging variants, their impact on immunity and effects on vaccine protection using animal models. We report the development of reagents, methodologies, models and notable findings facilitated by this collaborative approach and identify future challenges. This programme is a template for the response to rapidly evolving pathogens with pandemic potential by monitoring viral evolution in the human population to identify variants that could reduce the effectiveness of countermeasures.

Highly pathogenic H5N1 avian influenza (HPAI H5N1) viruses occasionally infect, but typically do not transmit, in mammals. In the spring of 2024, an unprecedented outbreak of HPAI H5N1 in bovine herds occurred in the USA, with virus spread within and between herds, infections in poultry and cats, and spillover into humans, collectively indicating an increased public health risk1–4. Here we characterize an HPAI H5N1 virus isolated from infected cow milk in mice and ferrets. Like other HPAI H5N1 viruses, the bovine H5N1 virus spread systemically, including to the mammary glands of both species, however, this tropism was also observed for an older HPAI H5N1 virus isolate. Bovine HPAI H5N1 virus bound to sialic acids expressed in human upper airways and inefficiently transmitted to exposed ferrets (one of four exposed ferrets seroconverted without virus detection). Bovine HPAI H5N1 virus thus possesses features that may facilitate infection and transmission in mammals.HPAI H5N1 virus isolated from infected cow milk is characterized in mice and ferrets, was inefficiently transmitted in ferrets, and bound to sialic acids expressed in human upper airways, showing features that may facilitate infection in mammals. [ABSTRACT FROM AUTHOR]

Ebola virus causes haemorrhagic fever with a high fatality rate in humans and non-human primates. It belongs to the family Filoviridae in the order Mononegavirales, which are viruses that contain linear, non-segmented, negative-sense, single-stranded genomic RNA.sup.1,2. The enveloped, filamentous virion contains the nucleocapsid, consisting of the helical nucleoprotein-RNA complex, VP24, VP30, VP35 and viral polymerase.sup.1,3. The nucleoprotein-RNA complex acts as a scaffold for nucleocapsid formation and as a template for RNA replication and transcription by condensing RNA into the virion.sup.4,5. RNA binding and nucleoprotein oligomerization are synergistic and do not readily occur independently.sup.6. Although recent cryo-electron tomography studies have revealed the overall architecture of the nucleocapsid core.sup.4,5, there has been no high-resolution reconstruction of the nucleocapsid. Here we report the structure of a recombinant Ebola virus nucleoprotein-RNA complex expressed in mammalian cells without chemical fixation, at near-atomic resolution using single-particle cryo-electron microscopy. Our structure reveals how the Ebola virus nucleocapsid core encapsidates its viral genome, its sequence-independent coordination with RNA by nucleoprotein, and the dynamic transition between the RNA-free and RNA-bound states. It provides direct structural evidence for the role of the N terminus of nucleoprotein in subunit oligomerization, and for the hydrophobic and electrostatic interactions that lead to the formation of the helical assembly. The structure is validated as representative of the native biological assembly of the nucleocapsid core by consistent dimensions and symmetry with the full virion.sup.5. The atomic model provides a detailed mechanistic basis for understanding nucleocapsid assembly and highlights key structural features that may serve as targets for anti-viral drug development.Near-atomic resolution cryo-electron microscopy structures of the Zaire ebolavirus nucleoprotein indicate a complex transition from the RNA-free to RNA-bound forms of the protein, and reveal the mechanism of oligomer formation and helical assembly., Author(s): Yukihiko Sugita [sup.1] [sup.7] , Hideyuki Matsunami [sup.1] , Yoshihiro Kawaoka [sup.2] [sup.3] [sup.4] , Takeshi Noda [sup.5] [sup.6] , Matthias Wolf [sup.1] Author Affiliations:(1) Molecular Cryo-Electron Microscopy Unit, [...]

Cell-surface-receptor binding by influenza viruses is a key determinant of their transmissibility, both from avian and animal species to humans as well as from human to human. Highly pathogenic avian [...]

Infection by Ebola virus can be fatal. The discovery of a human protein that mimics one type of Ebola protein and binds to another to suppress viral RNA production might aid the development of clinical treatments for the disease.The production of RNA by Ebola virus is suppressed by a human protein., Author(s): Seiya Yamayoshi, Yoshihiro KawaokaAuthor Affiliations:Host protein mimics viral protein to hinder infection by Ebola virus Ebola infection begins with fever, muscle pain and headache, followed by vomiting, diarrhoea, rash [...]

Influenza viruses cause annual epidemics and occasional pandemics that have claimed the lives of millions. The emergence of new strains will continue to pose challenges to public health and the scientific communities. A prime example is the recent emergence of swine-origin H1N1 viruses that have transmitted to and spread among humans, resulting in outbreaks internationally. Efforts to control these outbreaks and real-time monitoring of the evolution of this virus should provide us with invaluable information to direct infectious disease control programmes and to improve understanding of the factors that determine viral pathogenicity and/or transmissibility., The genomes of influenza viruses are plastic, owing to point mutations and reassortment events that contribute to the emergence of new variants or strains with epidemic or pandemic potential. Inasmuch, [...]

All viruses rely on host cell proteins and their associated mechanisms to complete the viral life cycle. Identifying the host molecules that participate in each step of virus replication could [...]

Author(s): Darwyn Kobasa [1]; Steven M. Jones [2, 3]; Kyoko Shinya [5]; John C. Kash [6]; John Copps [8]; Hideki Ebihara [2, 9, 10, 11]; Yasuko Hatta [12]; Jin Hyun [...]

Author(s): Shinya Yamada [1, 3]; Yasuo Suzuki [3, 4]; Takashi Suzuki [3, 5]; Mai Q. Le [6]; Chairul A. Nidom [7]; Yuko Sakai-Tagawa [1, 3]; Yukiko Muramoto [1, 3]; Mutsumi [...]

Author(s): Darwyn Kobasa [1, 10]; Ayato Takada [2, 3]; Kyoko Shinya [2, 10]; Masato Hatta [1]; Peter Halfmann [1]; Steven Theriault [4]; Hiroshi Suzuki [5]; Hidekazu Nishimura [6]; Keiko Mitamura [...]

Since the end of March 2013, avian influenza A viruses of the H7N9 subtype have caused more than 130 human cases of infection in China, many of which were severe, [...]

Author(s): Kyoko Shinya [1, 2, 4, 8]; Masahito Ebina [5]; Shinya Yamada [2]; Masao Ono [6]; Noriyuki Kasai [4]; Yoshihiro Kawaoka (corresponding author) [1, 2, 3, 7] Although more than [...]

Highly pathogenic avian H5N1 influenza viruses first proved lethal in humans in 1997 in Hong Kong. Since 2003, 578 confirmed infections have resulted in 340 deaths (go.nature.com/ epb7ts). Now widespread [...]

All viruses rely on host cell proteins and their associated mechanisms to complete the viral life cycle. Identifying the host molecules that participate in each step of virus replication could provide valuable new targets for antiviral therapy, but this goal may take several decades to achieve with conventional forward genetic screening methods and mammalian cell cultures. Here we describe a novel genome-wide RNA interference (RNAi) screen in Drosophila that can be used to identify host genes important for influenza virus replication. After modifying influenza virus to allow infection of Drosophila cells and detection of influenza virus gene expression, we tested an RNAi library against 13,071 genes (90% of the Drosophila genome), identifying over 100 for which suppression in Drosophila cells significantly inhibited or stimulated reporter gene (Renilla luciferase) expression from an influenza-virus-derived vector. The relevance of these findings to influenza virus infection of mammalian cells is illustrated for a subset of the Drosophila genes identified; that is, for three implicated Drosophila genes, the corresponding human homologues ATP6V0D1, COX6A1 and NXF1 are shown to have key functions in the replication of H5N1 and H1N1 influenza A viruses, but not vesicular stomatitis virus or vaccinia virus, in human HEK 293 cells. Thus, we have demonstrated the feasibility of using genome-wide RNAi screens in Drosophila to identify previously unrecognized host proteins that are required for influenza virus replication. This could accelerate the development of new classes of antiviral drugs for chemoprophylaxis and treatment, which are urgently needed given the obstacles to rapid development of an effective vaccine against pandemic influenza and the probable emergence of strains resistant to available drugs. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article on the resumption transmission studies for avian flu in the January 2012 issue.

The recent emergence of SARS-CoV-2 Omicron (B.1.1.529 lineage) variants possessing numerous mutations has raised concerns of decreased effectiveness of current vaccines, therapeutic monoclonal antibodies and antiviral drugs for COVID-19 against these variants 1,2 . The original Omicron lineage, BA.1, prevailed in many countries, but more recently, BA.2 has become dominant in at least 68 countries 3 . Here we evaluated the replicative ability and pathogenicity of authentic infectious BA.2 isolates in immunocompetent and human ACE2-expressing mice and hamsters. In contrast to recent data with chimeric, recombinant SARS-CoV-2 strains expressing the spike proteins of BA.1 and BA.2 on an ancestral WK-521 backbone 4 , we observed similar infectivity and pathogenicity in mice and hamsters for BA.2 and BA.1, and less pathogenicity compared with early SARS-CoV-2 strains. We also observed a marked and significant reduction in the neutralizing activity of plasma from individuals who had recovered from COVID-19 and vaccine recipients against BA.2 compared to ancestral and Delta variant strains. In addition, we found that some therapeutic monoclonal antibodies (REGN10987 plus REGN10933, COV2-2196 plus COV2-2130, and S309) and antiviral drugs (molnupiravir, nirmatrelvir and S-217622) can restrict viral infection in the respiratory organs of BA.2-infected hamsters. These findings suggest that the replication and pathogenicity of BA.2 is similar to that of BA.1 in rodents and that several therapeutic monoclonal antibodies and antiviral compounds are effective against Omicron BA.2 variants., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)