ABSTRACT
BACKGROUND/PURPOSE: A swine-origin influenza A/H1N1 virus (termed A/H1N1pdm) caused a pandemic in 2009 and has continuously circulated in the human population. To investigate its possible ecological effects on circulating influenza strains, the seasonal patterns of influenza viruses and the respective age distribution of infected patients were studies. METHODS: The data obtained from national influenza surveillance systems in Taiwan from July 2009 to June 2018 were analyzed. RESULTS: The A/H1N1pdm and A/H3N2 strains usually caused a higher ratio of severe to mild cases than influenza B. New variants of A/H1N1pdm and A/H3N2 emerged accompanied by a large epidemic peak. However, the new influenza B variants intended to circulate for several seasons before causing a large epidemic. The major group of outpatients affected by A/H1N1pdm were aged 13-23 years in the pandemic wave, and the age range of infected individuals gradually shifted to 24-49 and 0-6 years across seasons; A/H1N1pdm-infected inpatients were aged 24-49 years in 2009-2011, and the age range gradually switched to older groups aged 50-65 and >65 years. Individuals aged 0-6 or 24-49 years accounted for the majority of A/H3N2-infected outpatients across seasons, whereas most of the inpatients affected by A/H3N2 were aged >65 years. CONCLUSION: Understanding the effects of new variants and changes in dominant circulating viral strains on the age distribution of the affected human population, disease severity and epidemic levels is useful for the establishment of fine-tuned strategies for further improvement of influenza control.
Subject(s)
Influenza, Human/epidemiology , Seasons , Adolescent , Adult , Age Distribution , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Genetic Variation , Humans , Infant , Infant, Newborn , Influenza A Virus, H1N1 Subtype/genetics , Influenza A Virus, H1N1 Subtype/isolation & purification , Influenza A Virus, H3N2 Subtype/genetics , Influenza A Virus, H3N2 Subtype/isolation & purification , Influenza B virus/genetics , Influenza B virus/isolation & purification , Male , Middle Aged , Pandemics , Phylogeny , Taiwan/epidemiology , Young AdultABSTRACT
BACKGROUND: The epidemic of the 2016-2017 influenza season in Taiwan started early with moderate activity and was predominated by the influenza A(H3N2) virus. However, the influenza activity increased dramatically during the late stage of the 2016-2017 season. OBJECTIVES: The genetic and antigenic characteristics of the influenza A(H3N2) virus circulating in Taiwan during the 2016-2017 season were investigated. The relationship between virus clades and the patients' 2016-2017 vaccination histories was determined. STUDY DESIGN: Respiratory samples from patients with influenza-like illness in the community, clustered outbreaks, and inpatients with severe complications were tested for influenza virus. Influenza gene sequencing, phylogenetic analysis and hemagglutination inhibition assay were performed. RESULTS: A total of 1185, 690 and 353 cases of outpatients, inpatients and cluster events were tested positive for the A(H3N2) virus in this report. Multiple clades of the H3N2 virus co-circulated. New genetic variants were detected, including clade 3C.2a.1 with additional N121â¯K, K92R or T135â¯K mutations, 3C.2a.3a with T135â¯K and R150â¯K mutations and 3C.2a.4. The proportions of N121â¯K and T135â¯K mutations were continuously increasing. Most of the viruses (85.4%, 111/130) were antigenically related to the current vaccine strain. Infection by different clade H3N2 viruses did not correlate with immunization with the 2016-2017 vaccine. CONCLUSIONS: The data in this study indicate that antigenic drift is not the primary determinant of the epidemic wave at the end of the 2016-2017 season. The fitness changes in new variants, waning immunity and climatic changes are considered as possible contributors to the resurgence of the influenza A(H3N2) virus.
Subject(s)
Genetic Variation , Influenza A Virus, H3N2 Subtype/genetics , Influenza, Human/epidemiology , Influenza, Human/virology , Antigenic Variation , Hemagglutinin Glycoproteins, Influenza Virus/genetics , Hemagglutinin Glycoproteins, Influenza Virus/immunology , Humans , Influenza A Virus, H3N2 Subtype/classification , Influenza A Virus, H3N2 Subtype/isolation & purification , Mutation , Phylogeny , RNA, Viral/genetics , Sequence Analysis , Taiwan/epidemiology , Viral Proteins/genetics , Viral Proteins/immunologyABSTRACT
Retinoic acid inducible gene-I (RIG-I) is a cytosolic pathogen recognition receptor that initiates the immune response against many RNA viruses. Upon RNA ligand binding, RIG-I undergoes a conformational change facilitating its homo-oligomerization and activation that results in its translocation from the cytosol to intracellular membranes to bind its signaling adaptor protein, mitochondrial antiviral-signaling protein (MAVS). Here we show that RIG-I activation is regulated by reversible acetylation. Acetyl-mimetic mutants of RIG-I do not form virus-induced homo-oligomers, revealing that acetyl-lysine residues of the RIG-I repressor domain prevent assembly to active homo-oligomers. During acute infection, deacetylation of RIG-I promotes its oligomerization upon ligand binding. We identify histone deacetylase 6 (HDAC6) as the deacetylase that promotes RIG-I activation and innate antiviral immunity to recognize and restrict RNA virus infection.
