scholarly journals Novel Flu Viruses in Bats and Cattle: “Pushing the Envelope” of Influenza Infection

2018 ◽  
Vol 5 (3) ◽  
pp. 71 ◽  
Author(s):  
Suresh Kuchipudi ◽  
Ruth Nissly
Keyword(s):  
Infectious Disease ◽  
Influenza Virus ◽  
Host Range ◽  
Human Health ◽  
Influenza Infection ◽  
Influenza Viruses ◽  
Geographic Boundaries ◽  
Major Infectious Disease ◽  
Virus Host Range

Influenza viruses are among the major infectious disease threats of animal and human health. This review examines the recent discovery of novel influenza viruses in bats and cattle, the evolving complexity of influenza virus host range including the ability to cross species barriers and geographic boundaries, and implications to animal and human health.

scholarly journals RNA-Sequencing-Based Transcriptomic Analysis Reveals a Role for Annexin-A1 in Classical and Influenza A Virus-Induced Autophagy

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1399 ◽  
Author(s):  
Jianzhou Cui ◽  
Dhakshayini Morgan ◽  
Dao Han Cheng ◽  
Sok Lin Foo ◽  
Gracemary L. R. Yap ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A Virus ◽  
Influenza A ◽  
Influenza Infection ◽  
Critical Role ◽  
Mtor Inhibitors ◽  
Influenza Viruses ◽  
Annexin A1 ◽  
Underlying Mechanisms

Influenza viruses have been shown to use autophagy for their survival. However, the proteins and mechanisms involved in the autophagic process triggered by the influenza virus are unclear. Annexin-A1 (ANXA1) is an immunomodulatory protein involved in the regulation of the immune response and Influenza A virus (IAV) replication. In this study, using clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 (CRISPR associated protein 9) deletion of ANXA1, combined with the next-generation sequencing, we systematically analyzed the critical role of ANXA1 in IAV infection as well as the detailed processes governing IAV infection, such as macroautophagy. A number of differentially expressed genes were uniquely expressed in influenza A virus-infected A549 parental cells and A549 ∆ANXA1 cells, which were enriched in the immune system and infection-related pathways. Gene ontology and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway revealed the role of ANXA1 in autophagy. To validate this, the effect of mechanistic target of rapamycin (mTOR) inhibitors, starvation and influenza infection on autophagy was determined, and our results demonstrate that ANXA1 enhances autophagy induced by conventional autophagy inducers and influenza virus. These results will help us to understand the underlying mechanisms of IAV infection and provide a potential therapeutic target for restricting influenza viral replication and infection.

scholarly journals Influenza virus inhibits respiratory syncytial virus (RSV) infection via a two-wave expression of interferon-induced protein with tetratricopeptide (IFIT) proteins

2020 ◽  
Author(s):  
Yaron Drori ◽  
Jasmine Jacob-Hirsch ◽  
Rakefet Pando ◽  
Aharona Glatman-Freedman ◽  
Nehemya Friedman ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Influenza Virus ◽  
Respiratory Syncytial Virus ◽  
Influenza Infection ◽  
Treatment Strategies ◽  
Respiratory Viruses ◽  
Influenza Viruses ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Mouse Lungs

AbstractInfluenza viruses and respiratory syncytial virus (RSV) are respiratory viruses that primarily circulate worldwide during the autumn and winter seasons. Seasonal surveillance shows that RSV infection generally precedes influenza. However, in the last four winter seasons (2016-2020) an overlap of the morbidity peaks of both viruses was observed in Israel, and was paralleled by significantly lower RSV infection rates. To investigate whether the influenza virus inhibits RSV we performed coinfection of Human cervical carcinoma (HEp2) cells or mice with influenza and RSV and we observed that the influenza inhibited RSV growth, both in vitro and in vivo. Mass spectrometry analysis of mouse lungs infected with influenza identified a two-wave pattern of protein expression upregulation, which included members of the interferon-induced protein with tetratricopeptide (IFITs) family. Interestingly, in the second peak of upregulation, influenza viruses were no longer detectable in mouse lungs. We also observed that knockdown and overexpression of IFITs in HEp2 cells affected RSV multiplicity. In conclusion, influenza infection inhibits RSV infectivity via upregulation of IFIT proteins in a two-wave modality. Understanding of the interaction between influenza and RSV viruses and immune system involvement will contribute to the development and optimization of future treatment strategies against these viruses.Author SummaryRespiratory syncytial virus (RSV) and influenza viruses are both respiratory viruses associated with morbidity and mortality worldwide. RSV is usually detected in October, with a clear peak in December, whereas influenza virus arrives in November and peaks in January. In the last four seasons, influenza infection overlapped with that of RSV in Israel, which resulted in decreased morbidity of RSV suggesting that influenza virus inhibits RSV infection. To identify the mechanism responsible for the influenza inhibition of RSV we performed experiments in culture and in mice. We observed that influenza infection results in two wave modality of inhibition of RSV infection. Using mass spectrometry perfornmed on lungs from infected mice we show that influenza infection induces the expression of (IFIT) family of proteins which also showed a two-wave modality. Using knockdown and overexpression experiments we showed that indeed the IFTIs inhibits RSV infection. Our study provides new insights on the interaction between influenza and RSV viruses and immune system involvement and contribute to the development of future treatment strategies against these viruses.

scholarly journals A Global Perspective on H9N2 Avian Influenza Virus

Viruses ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 620 ◽  
Author(s):  
T(homas). P. Peacock ◽  
Joe James ◽  
Joshua E. Sealy ◽  
Munir Iqbal
Keyword(s):  
Influenza Virus ◽  
Avian Influenza ◽  
Avian Influenza Virus ◽  
Host Range ◽  
Influenza Viruses ◽  
Global Perspective ◽  
Zoonotic Infection ◽  
Avian Influenza Viruses ◽  
H9n2 Avian Influenza Virus ◽  
Global Spread

H9N2 avian influenza viruses have become globally widespread in poultry over the last two decades and represent a genuine threat both to the global poultry industry but also humans through their high rates of zoonotic infection and pandemic potential. H9N2 viruses are generally hyperendemic in affected countries and have been found in poultry in many new regions in recent years. In this review, we examine the current global spread of H9N2 avian influenza viruses as well as their host range, tropism, transmission routes and the risk posed by these viruses to human health.

scholarly journals Vaccination with virus-like particles containing hemagglutinin protects the lungs of mice with postifluenza bacterial pneumonia: virological, microbiological and clinical data

2020 ◽  
Vol 65 (3) ◽  
pp. 150-158
Author(s):  
I. N. Falynskova ◽  
A. Yu. Egorov ◽  
A. V. Poddubikov ◽  
N. O. Vartanova ◽  
N. P. Kartashova ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Clinical Data ◽  
Murine Model ◽  
Bacterial Pneumonia ◽  
Influenza Infection ◽  
Viral Disease ◽  
Influenza Viruses ◽  
Lung Damage ◽  
Virus Like Particles ◽  
Secondary Bacterial Pneumonia

Introduction. Influenza is a severe viral disease, a frequent complication of which is a secondary bacterial pneumonia. Influenza vaccines prevent secondary bacterial complications. Virus-like particles are one of the promising areas for the development of new vaccines. The aim of this work is to study the correlation of the pathomorphological characteristics of the lungs with clinical, virological, and microbiological markers of the disease at vaccination with virus-like particles (VLPs), containing hemagglutinin (HA) of influenza virus (HA-Gag-VLPs) in a murine model of secondary bacterial pneumonia induced by S. pneumoniae after influenza infection. Material and methods. BALB/c mice were vaccinated with VLPs containing influenza HA. After 21 days, mice were infected with two strains of influenza viruses, homologous and non-homologous, and 5 days after viral infection, were infected with S. pneumoniae. The vaccination effect was evaluated by morphological, virological (titer of the virus in the lungs) and microbiological (titer of bacteria in the lungs) data, and was confirmed by clinical data (survival, change in body weight). Results. Immunization with HA-Gag-VLPs, followed by infection with a homologous influenza virus and S. pneumoniae, reduced the area of foci of inflammation, inhibited the replication of the virus and bacteria in the lungs, and also protected animals from death and reduced their weight loss. Immunization with HA-Gag-VLPs upon infection with a heterologous strain and S. pneumoniae did not affect these criteria. Conclusion. The immunization with HA-Gag-VLPs prevented the viral replication, providing a reduction of S. pneumoniae titer and the degree of lung damage, protecting animals from the disease in a murine model of secondary bacterial pneumonia, induced by S. pneumoniae, after influenza infection with homologous strain of the virus.

scholarly journals Suppressor of cytokine signaling (SOCS)5 ameliorates influenza infection via inhibition of EGFR signaling

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Lukasz Kedzierski ◽  
Michelle D Tate ◽  
Alan C Hsu ◽  
Tatiana B Kolesnik ◽  
Edmond M Linossi ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Influenza Infection ◽  
Influenza Virus Infection ◽  
Growth Factor Receptor ◽  
Influenza Viruses ◽  
Cytokine Signaling ◽  
Virus Infections ◽  
Suppressor Of Cytokine Signaling ◽  
Inflammatory Conditions

Influenza virus infections have a significant impact on global human health. Individuals with suppressed immunity, or suffering from chronic inflammatory conditions such as COPD, are particularly susceptible to influenza. Here we show that suppressor of cytokine signaling (SOCS) five has a pivotal role in restricting influenza A virus in the airway epithelium, through the regulation of epidermal growth factor receptor (EGFR). Socs5-deficient mice exhibit heightened disease severity, with increased viral titres and weight loss. Socs5 levels were differentially regulated in response to distinct influenza viruses (H1N1, H3N2, H5N1 and H11N9) and were reduced in primary epithelial cells from COPD patients, again correlating with increased susceptibility to influenza. Importantly, restoration of SOCS5 levels restricted influenza virus infection, suggesting that manipulating SOCS5 expression and/or SOCS5 targets might be a novel therapeutic approach to influenza.

MiR-495 regulates cellular ROS levels by targeting sod2 to inhibit intracellular survival of Mycobacterium tuberculosis in macrophages

2021 ◽  
Author(s):  
Xuanxiu Ren ◽  
Wenqi Dong ◽  
Jiajia Feng ◽  
Pei Li ◽  
Yucheng Zheng ◽  
...  
Keyword(s):  
Infectious Disease ◽  
Mycobacterium Tuberculosis ◽  
Human Health ◽  
Theoretical Basis ◽  
Drug Targets ◽  
Early Stage ◽  
Intracellular Survival ◽  
Laboratory Research ◽  
Bacillus Calmette Guerin ◽  
Major Infectious Disease

Mycobacterium tuberculosis is a chronic infectious disease pathogen. To date, tuberculosis is a major infectious disease that endangers human health. To better prevent and treat tuberculosis, it is important to study the pathogenesis of M. tb . Based on early-stage laboratory research results, in this study, we verified the upregulation of sod2 in Bacillus Calmette–Guérin ( BCG ) and H37Rv infection. By detecting BCG / H37Rv intracellular survival in sod2 -silenced and sod2 - overexpressing macrophages, sod2 was found to promote the intracellular survival of BCG / H37Rv. Then, miR-495 was determined to be downregulated by BCG / H37Rv . BCG / H37Rv can upregulate sod2 expression by miR-495 to promote the intracellular survival of BCG / H37Rv through a decline in ROS levels. This study provides a theoretical basis for developing new drug targets and treating tuberculosis.

scholarly journals Matrix Protein 2 Extracellular Domain-Specific Monoclonal Antibodies Are an Effective and Potentially Universal Treatment for Influenza A

2020 ◽  
Author(s):  
Lynn Bimler ◽  
Sydney L. Ronzulli ◽  
Amber Y. Song ◽  
Scott K. Johnson ◽  
Cheryl A. Jones ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Monoclonal Antibodies ◽  
Human Health ◽  
Influenza A ◽  
Matrix Protein ◽  
Critical Role ◽  
Extracellular Domain ◽  
Influenza Viruses ◽  
Antigenic Drift ◽  
Protective Potential

Influenza virus infection causes significant morbidity and mortality worldwide. Humans fail to make a universally protective memory immune response to influenza A. Hemagglutinin and Neuraminidase undergo antigenic drift and shift, resulting in new influenza A strains to which humans are naive. Seasonal vaccines are often ineffective and escape mutants have been reported to all treatments for influenza A. In the absence of a universal influenza A vaccine or treatment, influenza A will remain a significant threat to human health. The extracellular domain of the M2-ion channel (M2e) is an ideal antigenic target for a universal therapeutic agent, as it is highly conserved across influenza A serotypes, has a low mutation rate, and is essential for viral entry and replication. Previous M2e-specific monoclonal antibodies (M2e-MAbs) show protective potential against influenza A, however, they are either strain specific or have limited efficacy. We generated seven murine M2e-MAbs and utilized in vitro and in vivo assays to validate the specificity of our novel M2e-MAbs and to explore the universality of their protective potential. Our data shows our M2e-MAbs bind to M2e peptide, HEK cells expressing the M2 channel, as well as, influenza virions and MDCK-ATL cells infected with influenza viruses of multiple serotypes. Our antibodies significantly protect highly influenza A virus susceptible BALB/c mice from lethal challenge with H1N1 A/PR/8/34, pH1N1 A/CA/07/2009, H5N1 A/Vietnam/1203/2004, and H7N9 A/Anhui/1/2013 by improving survival rates and weight loss. Based on these results, at least four of our seven M2e-MAbs show strong potential as universal influenza A treatments. IMPORTANCE Despite a seasonal vaccine and multiple therapeutic treatments, Influenza A remains a significant threat to human health. The biggest obstacle is producing a vaccine or treatment for influenza A is their universality or efficacy against not only seasonal variances in the influenza virus, but also against all human, avian, and swine serotypes and, therefore, potential pandemic strains. M2e has huge potential as a target for a vaccine or treatment against influenza A. It is the most conserved external protein on the virus. Antibodies against M2e have made it to clinical trials, but not succeeded. Here, we describe novel M2e antibodies produced in mice that are not only protective at low doses, but that we extensively test to determine their universality and found to be cross protective against all strains tested. Additionally, our work begins to elucidate the critical role of isotype for an influenza A monoclonal antibody therapeutic.

scholarly journals IMMUNOLOGICAL RELATIONSHIP BETWEEN THE SWINE AND HUMAN INFLUENZA VIRUSES IN SWINE

1937 ◽  
Vol 66 (2) ◽  
pp. 151-168 ◽  
Author(s):  
Richard E. Shope
Keyword(s):  
Influenza Virus ◽  
Influenza Infection ◽  
Swine Influenza Virus ◽  
Swine Influenza ◽  
Influenza Viruses ◽  
Human Influenza ◽  
Human Influenza Virus ◽  
Immunological Relationship ◽  
Cross Immunity ◽  
The Cross

Swine recovered from infection with either swine influenza or swine influenza virus alone are usually not only immune but refractory to human influenza infection. Swine recovered from infection with a mixture of human influenza virus and H. influenzae suis are usually immune to swine influenza while those recovered from infection with human influenza virus alone are usually not immune to swine influenza. The possible mechanisms involved in the cross-immunity between the influenza viruses are discussed.

scholarly journals PA Mutations Inherited during Viral Evolution Act Cooperatively To Increase Replication of Contemporary H5N1 Influenza Virus with an Expanded Host Range

2020 ◽  
Vol 95 (1) ◽  
Author(s):  
Yasuha Arai ◽  
Norihito Kawashita ◽  
Emad Mohamed Elgendy ◽  
Madiha Salah Ibrahim ◽  
Tomo Daidoji ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Avian Influenza ◽  
Host Range ◽  
Human Cells ◽  
Influenza Viruses ◽  
Human Adaptation ◽  
Avian Influenza Viruses ◽  
H5n1 Influenza

ABSTRACT Adaptive mutations and/or reassortments in avian influenza virus polymerase subunits PA, PB1, and PB2 are one of the major factors enabling the virus to overcome the species barrier to infect humans. The majority of human adaptation polymerase mutations have been identified in PB2; fewer adaptation mutations have been characterized in PA and PB1. Clade 2.2.1 avian influenza viruses (H5N1) are unique to Egypt and generally carry the human adaptation PB2-E627K substitution during their dissemination in nature. In this study, we identified other human adaptation polymerase mutations by analyzing phylogeny-associated PA mutations that H5N1 clade 2.2.1 viruses have accumulated during their evolution in the field. This analysis identified several PA mutations that produced increased replication by contemporary clade 2.2.1.2 viruses in vitro in human cells and in vivo in mice compared to ancestral clade 2.2.1 viruses. The PA mutations acted cooperatively to increase viral polymerase activity and replication in both avian and human cells, with the effect being more prominent in human cells at 33°C than at 37°C. These results indicated that PA mutations have a role in establishing contemporary clade 2.2.1.2 virus infections in poultry and in adaptation to infect mammals. Our study provided data on the mechanism for PA mutations to accumulate during avian influenza virus evolution and extend the viral host range. IMPORTANCE Clade 2.2.1 avian influenza viruses (H5N1) are unique to Egypt and have caused the highest number of human H5N1 influenza cases worldwide, presenting a serious global public health threat. These viruses may have the greatest evolutionary potential for adaptation from avian hosts to human hosts. Using a comprehensive phylogenetic approach, we identified several novel clade 2.2.1 virus polymerase mutations that increased viral replication in vitro in human cells and in vivo in mice. These mutations were in the polymerase PA subunit and acted cooperatively with the E627K mutation in the PB2 polymerase subunit to provide higher replication in contemporary clade 2.2.1.2 viruses than in ancestral clade 2.2.1 viruses. These data indicated that ongoing clade 2.2.1 dissemination in the field has driven PA mutations to modify viral replication to enable host range expansion, with a higher public health risk for humans.

scholarly journals Nasal mucus and influenza viruses. II. A new test for the presumptive diagnosis of influenza infection

1952 ◽  
Vol 50 (4) ◽  
pp. 491-501 ◽  
Author(s):  
S. Fazekas De St Groth
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Respiratory Diseases ◽  
Influenza Infection ◽  
Influenza Virus Infection ◽  
Acute Stage ◽  
Influenza Viruses ◽  
Presumptive Diagnosis ◽  
Nasal Mucus ◽  
Specificity And Sensitivity

Changes in the inhibitory properties of human nasal mucus were found to be positively correlated with objective signs of influenza virus infection during the 1950 epidemic. In approximately 80% of the cases the inhibitor index was significantly increased during the acute stage of the disease, and reverted to normal during convalescence.Various respiratory diseases other than epidemic influenza did not cause similar changes.Examination of the inhibitory pattern of nasal mucus is proposed as a presumptive test for influenza virus infection, and its merits are discussed under the headings of reproducibility, specificity and sensitivity.

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