influenza
Virus-Cell Interactions | SpotlightComprehensive Characterization of Transcriptional Activity during Influenza A Virus Infection Reveals Biases in Cap-Snatching of Host RNA SequencesInfection with influenza A virus (IAV) infection is responsible for an estimated 500,000 deaths and up to 5 million cases of severe respiratory illness each year. In this study, we looked at human primary immune cells (macrophages) infected with IAV. Our method allows us to look at both the host and the virus in parallel. We used these data to explore a process known as “cap-snatching,” where IAV snatches a short nucleotide sequence...
Pathogenesis and ImmunityThe Microbiota Contributes to the Control of Highly Pathogenic H5N9 Influenza Virus Replication in DucksDucks are frequently infected with avian influenza viruses belonging to multiple subtypes. They represent an important reservoir species of avian influenza viruses, which can occasionally be transmitted to other bird species or mammals, including humans. Ducks thus have a central role in the epidemiology of influenza virus infection. Importantly, ducks usually show little or no clinical signs even following infection with a highly...
Pathogenesis and ImmunityIRF5 Promotes Influenza Virus-Induced Inflammatory Responses in Human Induced Pluripotent Stem Cell-Derived Myeloid Cells and Murine ModelsThe inflammatory response to influenza A virus (IAV) participates in infection control but contributes to disease severity. After viral detection, intracellular pathways are activated, initiating cytokine production, but these pathways are incompletely understood. We show that interferon regulatory factor 5 (IRF5) mediates IAV-induced inflammation and, in mice, drives pathology. This was independent of antiviral type 1 IFN and virus...
Virus-Cell InteractionsModified Sialic Acids on Mucus and Erythrocytes Inhibit Influenza A Virus Hemagglutinin and Neuraminidase FunctionsSialic acids (Sia) are involved in numerous different cellular functions and are receptors for many pathogens. Sia come in chemically modified forms, but we lack a clear understanding of how they alter interactions with microbes. Here, we examine the expression of modified Sia in mouse tissues, on secreted mucus in saliva, and on erythrocytes, including those from IAV host species and animals used in IAV research. These Sia forms varied...
GemBenefits and Perils of Necroptosis in Influenza Virus InfectionInfluenza A viruses (IAV) are lytic viruses that have recently been found to activate necroptosis in many of the cell types they infect. Necroptotic cell death is potently immunogenic and limits IAV spread by directly eliminating infected cells and by mobilizing both innate and adaptive immune responses. The benefits of necroptosis to the host, however, may sometimes be outweighed by the potentially deleterious hyperinflammatory...
Pathogenesis and ImmunityHemagglutinin and Neuraminidase Antibodies Are Induced in an Age- and Subtype-Dependent Manner after Influenza Virus InfectionData on the immunologic responses to neuraminidase (NA) is lacking compared to what is available on hemagglutinin (HA) responses, despite growing evidence that NA immunity can be protective and broadly cross-reactive. Understanding these NA responses during natural infection is key to exploiting these properties for improving influenza vaccines. Using two community-acquired influenza cohorts, we showed that the induction of both HA and...
Structure and Assembly | SpotlightMapping of a Novel H3-Specific Broadly Neutralizing Monoclonal Antibody Targeting the Hemagglutinin Globular Head Isolated from an Elite Influenza Virus-Immunized Donor Exhibiting Serological BreadthInfluenza viruses escape immunity through continuous antigenic changes that occur predominantly on the viral hemagglutinin (HA). Induction of broadly neutralizing antibodies (bnAbs) targeting conserved epitopes following vaccination is a goal of universal influenza vaccines and advantageous in protecting hosts against virus evolution and antigenic drift. To date, most of the discovered bnAbs bind either to conserved sites in the stem...
Vaccines and Antiviral AgentsN-Linked Glycans and K147 Residue on Hemagglutinin Synergize To Elicit Broadly Reactive H1N1 Influenza Virus AntibodiesThere is a great need to develop broadly reactive or universal vaccines against influenza viruses. Advanced, next-generation hemagglutinin (HA) head-based vaccines that elicit protective antibodies against H1N1 influenza viruses have been developed. This study focused on understanding the specific amino acids around the receptor binding site (RBS) that were important in elicitation of these broadly reactive antibodies. Specific glycan...
Vaccines and Antiviral AgentsA Live Attenuated Influenza Vaccine Elicits Enhanced Heterologous Protection When the Internal Genes of the Vaccine Are Matched to Those of the Challenge VirusSeasonal influenza infection remains a major cause of disease and death, underscoring the need for improved vaccines. Among current influenza vaccines, the live attenuated influenza vaccine (LAIV) is unique in its ability to elicit T-cell immunity to the conserved internal proteins of the virus. Despite this, LAIV has shown limited efficacy in recent years. One possible reason is that the conserved, internal genes of all current LAIVs...
Virus-Cell InteractionsElucidating the Interactions between Influenza Virus Polymerase and Host Factor ANP32ASuccessful zoonotic transmission of influenza A virus into humans can lead to pandemics in an immunologically naive population. Host-encoded ANP32A proteins are required to support influenza A virus polymerase activity, and species differences in ANP32A can restrict the host range of influenza virus. Understanding how ANP32A proteins support the viral polymerase and how differences in ANP32A affect the ability of the polymerase to coopt...