Genetic research on influenza virus biology has been informed in large part by nucleotide variants present in seasonal or pandemic samples, or individual mutants generated in the laboratory, leaving a substantial part of the genome uncharacterized. Here, we have developed a single-nucleotide resolution genetic approach to interrogate the fitness effect of point mutations in 98% of the amino acid positions in the influenza A virus hemagglutinin (HA) gene. Our HA fitness map provides a reference to identify indispensable regions to aid in drug and vaccine design as targeting these regions will increase the genetic barrier for the emergence of escape mutations. This study offers a new platform for studying genome dynamics, structure-function relationships, virus-host interactions, and can further rational drug and vaccine design. Our approach can also be applied to any virus that can be genetically manipulated.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4018626 | PMC |
| http://dx.doi.org/10.1038/srep04942 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Deficient neutrophil responses early in influenza infection promote viral replication and pulmonary inflammation.
PLoS Pathog
January 2025
Graduate Program in Immunology, Ann Arbor, Michigan, United States of America.
Neutrophils play key protective roles in influenza infections, yet excessive neutrophilic inflammation is a hallmark of acute lung injury during severe infections. Phenotypic heterogeneity is increasingly recognized in neutrophil populations; however, how functional variation in neutrophils between individuals determine the diverse outcomes of influenza remains unclear. To examine immunologic responses that may drive varying outcomes in influenza, we infected C57BL/6 (B6) and A/J mice with mouse-adapted influenza A virus A/PR/8/34 H1N1.
View Article and Find Full Text PDFMucin Colocalizes with Influenza Virus and Preserves Infectivity in Deposited Model Respiratory Droplets.
Environ Sci Technol
January 2025
Department of Civil and Environmental Engineering, Virginia Tech, Blacksburg, Virginia 24061, United States.
The stability of influenza virus in respiratory particles varies with relative humidity (RH) and protein content. This study investigated the decay, or loss of infectivity, of influenza A virus (IAV) in 1-μL respiratory droplets deposited on a surface with varying concentrations of mucin, one of the most abundant proteins in respiratory mucus, and examined the localization of virions within droplets. IAV remained stable at 0.
View Article and Find Full Text PDFReaction-advection-diffusion model of highly pathogenic avian influenza with behavior of migratory wild birds.
J Math Biol
January 2025
School of Mathematics and Statistics, Northeast Normal University, 5268 Renmin Street, Changchun, 130024, Jilin, People's Republic of China.
Wild birds are one of the main natural reservoirs for avian influenza viruses, and their migratory behavior significantly influences the transmission of avian influenza. To better describe the migratory behavior of wild birds, a system of reaction-advection-diffusion equations is developed to characterize the interactions among wild birds, poultry, and humans. By the next-generation operator, the basic reproduction number of the model is formulated.
View Article and Find Full Text PDFBetter Outcomes for Ovarian Cancer Associated With the Detection of Anti-EBV TCR CDR3s: Potential Relevance to Diffuse Large B-Cell Lymphoma.
Am J Reprod Immunol
January 2025
Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida, USA.
Objectives: Given the ongoing challenges regarding the specific roles of viral infections in cancer etiology, or as cancer co-morbidities, this study assessed potential associations between anti-viral, T-cell receptor (TCR) complementarity domain region-3 (CDR3s), and clinical outcomes for ovarian cancer.
Methods: TCR CDR3s were isolated from ovarian cancer specimens for a determination of which patients had anti-viral CDR3s and whether those patients had better or worse outcomes.
Results: Analyses revealed that patients with exact matches of anti-Epstein-Barr virus (EBV) CDR3 amino acid sequences exhibited better outcomes for both overall and disease-specific survival.
Cigarette smoke components modulate the MR1-MAIT axis.
J Exp Med
February 2025
Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Australia.
Tobacco smoking is prevalent across the world and causes numerous diseases. Cigarette smoke (CS) compromises immunity, yet little is known of the components of CS that impact T cell function. MR1 is a ubiquitous molecule that presents bacterial metabolites to MAIT cells, which are highly abundant in the lungs.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!