Effects of Cigarette Smoking on Influenza Virus/Host Interplay

Cigarette smoking has been shown to increase the risk of respiratory infection, resulting in the exacerbation of infectious disease outcomes. Influenza viruses are a major respiratory viral pathogen, which are responsible for yearly epidemics that result in between 20,000 and 50,000 deaths in the US alone. However, there are limited general summaries on the impact of cigarette smoking on influenza pathogenic outcomes. Here, we will provide a systematic summarization of the current understanding of the interplay of smoking and influenza viral infection with a focus on examining how cigarette smoking affects innate and adaptive immune responses, inflammation levels, tissues that contribute to systemic chronic inflammation, and how this affects influenza A virus (IAV) disease outcomes. This summarization will: (1) help to clarify the conflict in the reports on viral pathogenicity; (2) fill knowledge gaps regarding critical anti-viral defenses such as antibody responses to IAV; and (3) provide an updated understanding of the underlying mechanism behind how cigarette smoking influences IAV pathogenicity.

Neutrophils and Influenza: A Thin Line between Helpful and Harmful

Influenza viruses are one of the most prevalent respiratory pathogens known to humans and pose a significant threat to global public health each year. Annual influenza epidemics are responsible for 3–5 million infections worldwide and approximately 500,000 deaths. Presently, yearly vaccinations represent the most effective means of combating these viruses. In humans, influenza viruses infect respiratory epithelial cells and typically cause localized infections of mild to moderate severity. Neutrophils are the first innate cells to be recruited to the site of the infection and possess a wide range of effector functions to eliminate viruses. Some well-described effector functions include phagocytosis, degranulation, the production of reactive oxygen species (ROS), and the formation of neutrophil extracellular traps (NETs). However, while these mechanisms can promote infection resolution, they can also contribute to the pathology of severe disease. Thus, the role of neutrophils in influenza viral infection is nuanced, and the threshold at which protective functions give way to immunopathology is not well understood. Moreover, notable differences between human and murine neutrophils underscore the need to exercise caution when applying murine findings to human physiology. This review aims to provide an overview of neutrophil characteristics, their classic effector functions, as well as more recently described antibody-mediated effector functions. Finally, we discuss the controversial role these cells play in the context of influenza virus infections and how our knowledge of this cell type can be leveraged in the design of universal influenza virus vaccines.

Modelling the Effect of MUC1 on Influenza Virus Infection Kinetics and Macrophage Dynamics

MUC1 belongs to the family of cell surface (cs-) mucins. Experimental evidence indicates that its presence reduces in vivo influenza viral infection severity. However, the mechanisms by which MUC1 influences viral dynamics and the host immune response are not yet well understood, limiting our ability to predict the efficacy of potential treatments that target MUC1. To address this limitation, we use available in vivo kinetic data for both virus and macrophage populations in wildtype and MUC1 knockout mice. We apply two mathematical models of within-host influenza dynamics to this data. The models differ in how they categorise the mechanisms of viral control. Both models provide evidence that MUC1 reduces the susceptibility of epithelial cells to influenza virus and regulates macrophage recruitment. Furthermore, we predict and compare some key infection-related quantities between the two mice groups. We find that MUC1 significantly reduces the basic reproduction number of viral replication as well as the number of cumulative macrophages but has little impact on the cumulative viral load. Our analyses suggest that the viral replication rate in the early stages of infection influences the kinetics of the host immune response, with consequences for infection outcomes, such as severity. We also show that MUC1 plays a strong anti-inflammatory role in the regulation of the host immune response. This study improves our understanding of the dynamic role of MUC1 against influenza infection and may support the development of novel antiviral treatments and immunomodulators that target MUC1.

Modelling The Effect of MUC1 on Influenza Virus Infection Kinetics and Macrophage Dynamics

MUC1 belongs to the family of cell surface (cs-) mucins. Experimental evidence indicates that its presence reduces in vivo influenza viral infection severity. However, the mechanisms by which MUC1 influences viral dynamics and the host immune response are not yet well understood, limiting our ability to predict the efficacy of potential treatments that target MUC1. To address this limitation, we utilize available in vivo kinetic data for both virus and macrophage populations in wildtype and MUC1 knockout mice. We apply two mathematical models of within-host influenza dynamics to this data. The models differ in how they categorise the mechanisms of viral control. Both models provide evidence that MUC1 reduces the susceptibility of epithelial cells to influenza virus and regulates macrophage recruitment. Furthermore, we predict and compare some key infection-related quantities between the two mice groups. We find that MUC1 significantly reduces the basic reproduction number of viral replication as well as the number of cumulative macrophages but has little impact on the cumulative viral load. Our analyses suggest that the viral replication rate in the early stages of infection influences the kinetics of the host immune response, with consequences for infection outcomes, such as severity. We also show that MUC1 plays a strong anti-inflammatory role in the regulation of the host immune response. This study improves our understanding of the dynamic role of MUC1 against influenza infection and may support the development of novel antiviral treatments and immunomodulators that target MUC1.

Influenza causes alterations to oligodendrocyte-specific transcripts and the myelin lipidome in the adult mouse central nervous system.

The notion that myelin remains static during adulthood has been challenged in recent years. Myelin is not only crucial for proper cognitive function and behavior, but it is vulnerable to alterations from external factors outside the window of development. Here, in the adult mouse CNS, RNA analysis revealed global downregulation and subsequent recovery of oligodendrocyte-specific transcripts in response to peripheral influenza viral infection. Furthermore, shot-gun lipidomic analysis revealed that infection alters the lipid profile in the prefrontal cortex as well as in purified brain myelin. Finally, treatment with the colony stimulating factor receptor (CSFR)1 antagonist GW2580 during infection suppressed glial activation and partially restored oligodendrocyte-specific myelin transcripts to baseline levels. Together, these findings reveal a yet unforeseen consequence of peripheral infection on oligodendrocyte homeostasis in the adult mouse.

Mitochondrial morphodynamics alteration induced by influenza virus infection as a new antiviral strategy

Influenza virus infections are major public health threats due to their high rates of morbidity and mortality. Upon influenza virus entry, host cells experience modifications of endomembranes, including those used for virus trafficking and replication. Here we report that influenza virus infection modifies mitochondrial morphodynamics by promoting mitochondria elongation and altering endoplasmic reticulum-mitochondria tethering in host cells. Expression of the viral RNA recapitulates these modifications inside cells. Virus induced mitochondria hyper-elongation was promoted by fission associated protein DRP1 relocalization to the cytosol, enhancing a pro-fusion status. We show that altering mitochondrial hyper-fusion with Mito-C, a novel pro-fission compound, not only restores mitochondrial morphodynamics and endoplasmic reticulum-mitochondria contact sites but also dramatically reduces influenza replication. Finally, we demonstrate that the observed Mito-C antiviral property is directly connected with the innate immunity signaling RIG-I complex at mitochondria. Our data highlight the importance of a functional interchange between mitochondrial morphodynamics and innate immunity machineries in the context of influenza viral infection.

Epidemiological Study of Influenza A(H1N1) Virus Infection during Lockdown Due to COVID-19 Pandemics in Uttarakhand

Objectives: The purpose of this research was to study the epidemiology of H1N1 influenza A virus infection during lockdown due to COVID-19 pandemic in Uttarakhand. Methodology: An analysis of primary data, obtained from DNA Labs-A Center for Applied Sciences, Dehradun after detection of the throat and nasal swabs by RT-PCR method. The total number of samples were 102 which were collected from the suspected cases for influenza like illness (ILI) in and around Uttarakhand region in different age groups. Molecular Characterization was done for all the cases. The data contained the cases from the month of March, 2020 to the month of November, 2020. Results: Results showed that after the onset of lockdown, the number of positive cases for H1N1 influenza viral infection were less in comparative to the negative cases (30 positive cases and 72 negative cases). Age group from 21 to 40 years and above 70 years became infected with the H1N1 swine flu and suffered with Category C symptom. Conclusions: This research provides the significant findings for the epidemiological study of H1N1 influenza viral infection during lockdown due to COVID-19 pandemics in Uttarakhand. It could be said that due to the similarities of the symptoms of H1N1 influenza A virus and COVID-19, all the cases were referred to COVID-19 testing due to its impact even though that case could have been suffering from any other disease including H1N1 as the symptoms similarities between these two viruses are almost the same.