Influenza virus articles within Nature Communications

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  • Article
    | Open Access

    Ageing has been associated with impaired function of alveolar macrophages and increased susceptibility, mortality and complications as a result of viral infection. Here, the authors show that prostaglandin E2 is one of the factors responsible for impairing immune defences against influenza during ageing.

    • Judy Chen
    • , Jane C. Deng
    •  & Daniel R. Goldstein

  • Article
    | Open Access

    Broadly protective antibodies targeting influenza viruses are of interest as potential therapeutics or to inform vaccine development. Here the authors characterize a human mAb (DA03E17) with heterosubtypic binding to neuraminidases from IAVs and IBVs that provides broad protection in vitro and in vivo.

    • Atsuhiro Yasuhara
    • , Seiya Yamayoshi
    •  & Yoshihiro Kawaoka

  • Article
    | Open Access

    Identification of host antiviral restriction factors could provide targets for antiviral therapy. Here, using a genome-wide CRISPR screen, the authors identify the glycosyltransferase B3GAT1 as a host protein which, when ectopically overexpressed, restricts influenza virus infection in vitro and in mice, as well as other viruses relying on sialic acid for entry.

    • Joseph D. Trimarco
    • , Sarah L. Nelson
    •  & Nicholas S. Heaton

  • Article
    | Open Access

    Influenza A virus (IAV) nonstructural protein 1 (NS1) is a multifunctional virulence factor that interacts with several host factors such as phosphatidylinositol-3-kinase (PI3K). NS1 binds specifically to the p85β regulatory subunit of PI3K and subsequently activates PI3K signaling. Here, Kim et al. show that functionally near-neutral, strain-specific NS1 mutations lead to variations in binding kinetics to p85β exhibit long-range epistatic interactions. Applying NMR they provide evidence that the structural dynamics of the NS1 hydrophobic core have evolved over time and contributed to epistasis.

    • Iktae Kim
    • , Alyssa Dubrow
    •  & Jae-Hyun Cho

  • Article
    | Open Access

    Circulating subtypes of Influenza viruses seasonally change and therefore vaccines need to be matched to these strains each year, which is why there is a need for next-generation vaccines that can elicit broad and cross-type protection. Here, Li et al. generate a human-mouse chimeric antibody with broad neutralizing activity against seasonal and pandemic H1N1 and some H5N1 viruses in vivo and identify residues on hemagglutinin relevant for its broad neutralization activity.

    • Tingting Li
    • , Junyu Chen
    •  & Ningshao Xia

  • Article
    | Open Access

    The public health concern caused by influenza B virus is often overlooked, yet represents a significant global burden. Here, the authors evaluate the cellular and humoral immune responses of multivalent vaccine candidates, based on the lipid nanoparticle-encapsulated nucleoside-modified mRNA platform, and demonstrate protection of mice from challenge with a broad panel of influenza B viruses.

    • Norbert Pardi
    • , Juan Manuel Carreño
    •  & Meagan McMahon

  • Article
    | Open Access

    It is believed that human Influenza HA glycoprotein attaches to alpha2-6 linked sialic acids (SA) on cells, while avian viruses bind to alpha2-3 linked sialic acids, therewith contributing to host tropism. Here, Liu et al. show that mixing low-affinity alpha2-3 SA with low amounts of high-affinity alpha2-6 SA increases binding and entry of human viruses and the converse for avian virus. This shows that receptor recognition is not as strict as currently assumed and provides evidence that heteromultivalent interactions between human/avian HA and SA contributes to host adaptation.

    • Mengying Liu
    • , Liane Z. X. Huang
    •  & Erik de Vries

  • Article
    | Open Access

    Transmission of influenza A viruses (IAV) between hosts and replication within host impose genetic bottlenecks, constraining viral diversity and adaptation. Here, Amato et al. perform site-specific inoculation of barcoded IAV of ferrets and track viral diversity as infection spreads to the lower respiratory tract and conclude that narrow population bottlenecks are an important feature of the within-host infection dynamics.

    • Katherine A. Amato
    • , Luis A. Haddock III
    •  & Andrew Mehle

  • Article
    | Open Access

    For archival pathogens, like pH1N1 Influenza A virus the causative agent of 1918/19 pandemic, only few whole genome sequences exist. Here, Patrono et al. provide one complete and two partial genomes from Germany and find variation in two sites in the nucleoprotein gene in pandemic samples compared to pre-pandemic samples, that are associated with resistance to host antiviral response, pointing at a possible viral adaptation to humans.

    • Livia V. Patrono
    • , Bram Vrancken
    •  & Sébastien Calvignac-Spencer

  • Article
    | Open Access

    While most broadly neutralizing antibodies (bnAb) against Influenza virus target conserved conformational epitopes of the glycoprotein hemagglutinin (HA), Sun et al. characterize a lineage of bnAbs that neutralize group 1 and 2 strains. Structural characterization shows that antibody 28-12 binds a continuous epitope within H3 (group 2) but requires a conformational epitope for H1 (group 1) binding. Comparison of germline-reverted Ab and intermediate mutants provides evidence for an evolutionary adaptation from group 2 to group 1 strain.

    • Xiaoyu Sun
    • , Caixuan Liu
    •  & Bing Sun

  • Article
    | Open Access

    Here, Zhao et al. characterize the anti-viral effect of the compound APL-16-5, which is originally derived from the plant endophytic fungus Aspergillus, on Influenza A virus infection in vitro and in vivo. They find that APL-16-5 binds to the E3 ligase TRIM25 and viral polymerase subunit PA and therewith mediates ubiquitination of PA and subsequent proteasome-mediated degradation.’

    • Jianyuan Zhao
    • , Jing Wang
    •  & Shan Cen

  • Article
    | Open Access

    Influenza virus neuraminidase (NA) is a drug target and a potential vaccine antigen. Here, the authors provide a detailed analysis of the conformational stability of NA, and show how expression and stability of recombinant NA antigens can be strengthened through structure-based design.

    • Daniel Ellis
    • , Julia Lederhofer
    •  & Masaru Kanekiyo

  • Article
    | Open Access

    Serological classification of influenza infection has classically been based on a four-fold or higher increase in antibody levels, but this approach may not be optimal. Here, the authors develop a Bayesian model to improve identification of infections in serological samples by accounting for individual antibody dynamics.

    • Tim K. Tsang
    • , Ranawaka A. P. M. Perera
    •  & Simon Cauchemez

  • Article
    | Open Access

    Here Wraith et al. report homotypic protection from repeated influenza infection in a prospective pediatric cohort in Nicaragua followed for 9 years. This protection is observed across multiple seasons, subtypes, and lineages and is consistent for older and younger children.

    • Steph Wraith
    • , Angel Balmaseda
    •  & Aubree Gordon

  • Article
    | Open Access

    Influenza viruses carry their own RNAdependent RNA-polymerase that is highly conserved and a promising anti-viral target. Combining functional and structural data, Keown et al. characterise the inhibitory effect of nanobodies on 1918 pandemic H1N1 influenza strain polymerase complex and identify sensitive sites interfering with polymerase activity in vitro.

    • Jeremy R. Keown
    • , Zihan Zhu
    •  & Jonathan M. Grimes

  • Article
    | Open Access

    Multi-strain pathogens, such as influenza, present challenges for interpretation of seroprevalence data as estimates may vary by strain. Here, the authors develop a method for estimating age-specific seroprevalence based on principal components analysis and apply it to influenza data from Vietnam.

    • Dao Nguyen Vinh
    • , Nguyen Thi Duy Nhat
    •  & Maciej F. Boni

  • Article
    | Open Access

    The recently identified Wuhan spiny eel influenza virus (WSEIV) sequence is more closely related to influenza B than A viruses. Here, the authors functionally characterize the putative surface glycoproteins of WSEIV and show that its NA-like protein has sialidase activity and its HA-like protein binds monosialic ganglioside 2.

    • Guha Asthagiri Arunkumar
    • , Disha Bhavsar
    •  & Florian Krammer

  • Article
    | Open Access

    Influenza A virus (IAV) and SARS-CoV-2 coinfection is a possible scenario during influenza season. Here, the authors show in a mouse model that IAV infection increases the risk of severe disease upon SARS-CoV-2 infection two days later. IAV vaccination, especially antibody-dependent, protects from severe disease during coinfection.

    • Hagit Achdout
    • , Einat. B. Vitner
    •  & Tomer Israely

  • Article
    | Open Access

    Here, Broszeit et al. show that circulating A/H3N2 viruses have evolved binding specificity to α2,6-sialosides on extended LacNAc moieties and therefore cannot agglutinate erythrocytes. Applying glycan remodeling allows to install functional receptors on erythrocytes and promotes identification of newly circulating variants to facilitate vaccine design.

    • Frederik Broszeit
    • , Rosanne J. van Beek
    •  & Geert-Jan Boons

  • Article
    | Open Access

    Influenza forecasting in the United States is challenging and consequential, with the ability to improve the public health response. Here the authors show the performance of the multiscale flu forecasting model, Dante, that won the CDC’s 2018/19 national, regional and state flu forecasting challenges.

    • Dave Osthus
    •  & Kelly R. Moran

  • Article
    | Open Access

    The immunology of Indigenous populations is generally understudied outside the context of diseases that are prevalent in these communities. Here the authors identify prevalence of influenza CD8+ T cell epitopes in an Indigenous Australian population expressing the susceptibility allomorph HLA A*24:02 and validate immunodominance of some of these epitopes in mice.

    • Luca Hensen
    • , Patricia T. Illing
    •  & Katherine Kedzierska

  • Article
    | Open Access

    Understanding the human antibody response to influenza A virus strains is important for vaccine development. Here, Creanga et al. generate a panel of 55 replication-deficient reporter viruses representing diversity of human H1N1 and H3N2, and pandemic subtypes and characterize the neutralization profile of 24 antibodies and polyclonal sera.

    • Adrian Creanga
    • , Rebecca A. Gillespie
    •  & Masaru Kanekiyo

  • Article
    | Open Access

    Influenza C virus contains a single surface glycoprotein, the haemagglutinin-esterase-fusion (HEF) protein, that mediates receptor binding, receptor destruction, and membrane fusion activities. Here, the authors apply electron cryotomography of whole virus together with subtomogram averaging to determine the HEF structure and lattice organisation on the viral membrane and they discuss mechanistic implications for virus budding and membrane fusion.

    • Steinar Halldorsson
    • , Kasim Sader
    •  & Peter B. Rosenthal

  • Article
    | Open Access

    New Zealand has been relatively successful in controlling COVID-19 due to implementation of strict non-pharmaceutical interventions. Here, the authors demonstrate a striking decline in reports of influenza and other non-influenza respiratory pathogens over winter months in which the interventions have been in place.

    • Q. Sue Huang
    • , Tim Wood
    •  & Richard J. Webby

  • Article
    | Open Access

    Human mobility plays a central role in the spread of infectious diseases and can help in forecasting incidence. Here the authors show a comparison of multiple mobility benchmarks in forecasting influenza, and demonstrate the value of a machine-learned mobility map with global coverage at multiple spatial scales.

    • Srinivasan Venkatramanan
    • , Adam Sadilek
    •  & Madhav Marathe

  • Article
    | Open Access

    Previously, a broadly neutralizing antibody, 3I14, active against groups 1 and 2 influenza A viruses was isolated from human memory B cells and showed protection in mice from lethal viral challenge. Here, Harshbarger and Deming et al. provide the crystal structure of 3I14 Fab in complex with H3, H6, and H10.

    • Wayne D. Harshbarger
    • , Derrick Deming
    •  & Wayne A. Marasco

  • Article
    | Open Access

    In this study, the authors present a genomic surveillance of avian influenza genomes sampled from live poultry markets in China. They report that a number of variants have emerged since 2016 that pose an increased risk to humans. They highlight the importance of continuous genome surveillance of circulating influenza strains.

    • Yuhai Bi
    • , Juan Li
    •  & Weifeng Shi

  • Article
    | Open Access

    In this study, the authors combine an anti-viral drug and immune system inducer to treat influenza A and B viral infections in vitro and in vivo. They show that the compound outperforms zanamivir alone as it is still able to clear infection three days post infection, and it can be administered via different routes without reduced efficacy.

    • Xin Liu
    • , Boning Zhang
    •  & Philip S. Low

  • Article
    | Open Access

    Highly pathogenic avian influenza viruses (HPAIV) can evolve via acquisition of polybasic cleavage sites, but the contribution of other mutations remains unclear. Here, the authors combine phylogenetic, statistical and structural approaches, and identify parallel mutations that are associated with HPAIV phenotype.

    • Marina Escalera-Zamudio
    • , Michael Golden
    •  & Oliver G. Pybus

  • Article
    | Open Access

    Influenza exposure in early childhood can affect the immune response to distinct viral strains later in life. Here, Gouma et al. show that contemporary 3c2.A H3N2 virus infections boost non-neutralizing H3N2 antibodies in middle-aged individuals, potentially leaving them vulnerable to recurrent infections.

    • Sigrid Gouma
    • , Kangchon Kim
    •  & Scott E. Hensley

  • Article
    | Open Access

    The mechanism underlying packaging of the 8 segments of the influenza virus genome into virions is not well understood. Here, the authors use a multiplexed FISH assay to monitor the 8 segments in parallel in infected cells suggesting bundling routes during the packaging process.

    • Ivan Haralampiev
    • , Simon Prisner
    •  & Andreas Herrmann

  • Article
    | Open Access

    Here Zhao et al. report a promising broad-spectrum antiviral alkaline peptide—P9R—that is active against several respiratory, pH-dependent viruses, including Influenza and SARS-CoV-2. P9R interferes with virus internalization by binding to the virus and subsequent inhibition of endosomal acidification.

    • Hanjun Zhao
    • , Kelvin K. W. To
    •  & Kwok-Yung Yuen

  • Article
    | Open Access

    Influenza viruses are believed to transmit through the air as respiratory droplets or aerosols. In the guinea pig model, Asadi et al. show that influenza virus can also be transmitted as aerosolized fomites, which are microscopic dust particles stirred up from a virus-contaminated environment.

    • Sima Asadi
    • , Nassima Gaaloul ben Hnia
    •  & Nicole M. Bouvier

  • Article
    | Open Access

    Avian influenza polymerase undergoes host adaptation in order to efficiently replicate in human cells. Here, the authors use NMR spectroscopy and quantitative ensemble modelling to describe the highly dynamic assemblies formed by the human-adapted or avian-adapted C-terminal domains with the respective ANP32A host proteins.

    • Aldo R. Camacho-Zarco
    • , Sissy Kalayil
    •  & Martin Blackledge

  • Article
    | Open Access

    Seasonal influenza epidemics vary in timing and size, but the causes of the variation remain unclear. Here, the authors analyse a 15-year city-level data set, and find that fluctuations in climatic factors do not predict onset timing, and that while antigenic change does not have a consistent effect on epidemic size, the timing of onset and heterosubtypic competition do.

    • Edward K. S. Lam
    • , Dylan H. Morris
    •  & Colin A. Russell

  • Article
    | Open Access

    Influenza A virus (IAV) infection can be exacerbated by bacterial co-infections but the effect of IAV on the upper respiratory tract (URT) microbiome remains unclear. Here, the authors compare the dynamics of the UTR microbiome in IAV-infected ferrets and humans, finding similar trends at the ecosystem and individual taxon level in both hosts.

    • Drishti Kaul
    • , Raveen Rathnasinghe
    •  & Rafael A. Medina

  • Article
    | Open Access

    Vaccine mismatch and changes in antigenicity due to vaccine strain egg adaptation can affect seasonal influenza vaccine effectiveness. Here, Gouma et al. show that the egg-adapted 3c3.A H3N2 vaccine strain elicits antibodies with limited reactivity to a wildtype 3c3.A strain and currently circulating 3c2.A H3N2 strains.

    • Sigrid Gouma
    • , Madison Weirick
    •  & Scott E. Hensley

  • Article
    | Open Access

    Antigenic site B in influenza A virus hemagglutinin (HA) is immunodominant in circulating human H3N2 strains. Using deep mutational scanning, Wu et al. here define the local fitness landscapes of HA antigenic site B in six human H3N2 strains, providing insights into evolvability of influenza antigenicity.

    • Nicholas C. Wu
    • , Jakub Otwinowski
    •  & Ian A. Wilson

  • Article
    | Open Access

    Here, the authors perform simultaneous inoculation of genetically tagged influenza A virus in ferrets and show that airborne transmissible viruses are preferentially transmitted from the upper respiratory tract, which correlates with high replication ability in the ferret and human nasal respiratory epithelium.

    • Mathilde Richard
    • , Judith M. A. van den Brand
    •  & Sander Herfst

  • Article
    | Open Access

    Influenza virus hemagglutinin (HA) stem between group 1 and 2 viruses has different glycosylation patterns, likely hampering cross-group protection. Here, Boyoglu-Barnum et al. show that introducing a group 2 glycan into a group 1 stem nanoparticle vaccine broadens antibody responses in mice to cross-react with group 2 HAs.

    • Seyhan Boyoglu-Barnum
    • , Geoffrey B. Hutchinson
    •  & Masaru Kanekiyo

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