scholarly journals Using Zebrafish Models of Human Influenza A Virus Infections to Screen Antiviral Drugs and Characterize Host Immune Cell Responses

10.3791/55235 ◽  
2017 ◽  
Author(s):  
Con Sullivan ◽  
Denise Jurcyzszak ◽  
Michelle F. Goody ◽  
Kristin A. Gabor ◽  
Jacob R. Longfellow ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Immune Cell ◽  
Antiviral Drugs ◽  
Virus Infections ◽  
Human Influenza ◽  
Cell Responses ◽  
Host Immune Cell

scholarly journals Demographic and ecological risk factors for human influenza A virus infections in rural Indonesia

2017 ◽  
Vol 11 (5) ◽  
pp. 425-433 ◽  
Author(s):  
Elisabeth Dowling Root ◽  
Dwi Agustian ◽  
Cissy Kartasasmita ◽  
Timothy M. Uyeki ◽  
Eric A. F. Simões
Keyword(s):  
Risk Factors ◽  
Influenza A Virus ◽  
Ecological Risk ◽  
Influenza A ◽  
Virus Infections ◽  
Human Influenza ◽  
Ecological Risk Factors

scholarly journals Differential Recognition of Influenza A Viruses by M158–66Epitope-Specific CD8+T Cells Is Determined by Extraepitopic Amino Acid Residues

2015 ◽  
Vol 90 (2) ◽  
pp. 1009-1022 ◽  
Author(s):  
Carolien E. van de Sandt ◽  
Joost H. C. M. Kreijtz ◽  
Martina M. Geelhoed-Mieras ◽  
Nella J. Nieuwkoop ◽  
Monique I. Spronken ◽  
...  
Keyword(s):  
Amino Acid ◽  
Influenza A Virus ◽  
Influenza A ◽  
Rational Design ◽  
Amino Acid Residues ◽  
Virus Infections ◽  
Human Influenza ◽  
Influenza A Viruses ◽  
Specific Ctls ◽  
Naturally Occurring

ABSTRACTNatural influenza A virus infections elicit both virus-specific antibody and CD4+and CD8+T cell responses. Influenza A virus-specific CD8+cytotoxic T lymphocytes (CTLs) contribute to clearance of influenza virus infections. Viral CTL epitopes can display variation, allowing influenza A viruses to evade recognition by epitope-specific CTLs. Due to functional constraints, some epitopes, like the immunodominant HLA-A*0201-restricted matrix protein 1 (M158–66) epitope, are highly conserved between influenza A viruses regardless of their subtype or host species of origin. We hypothesized that human influenza A viruses evade recognition of this epitope by impairing antigen processing and presentation by extraepitopic amino acid substitutions. Activation of specific T cells was used as an indication of antigen presentation. Here, we show that the M158–66epitope in the M1 protein derived from human influenza A virus was poorly recognized compared to the M1 protein derived from avian influenza A virus. Furthermore, we demonstrate that naturally occurring variations at extraepitopic amino acid residues affect CD8+T cell recognition of the M158–66epitope. These data indicate that human influenza A viruses can impair recognition by M158–66-specific CTLs while retaining the conserved amino acid sequence of the epitope, which may represent a yet-unknown immune evasion strategy for influenza A viruses. This difference in recognition may have implications for the viral replication kinetics in HLA-A*0201 individuals and spread of influenza A viruses in the human population. The findings may aid the rational design of universal influenza vaccines that aim at the induction of cross-reactive virus-specific CTL responses.IMPORTANCEInfluenza viruses are an important cause of acute respiratory tract infections. Natural influenza A virus infections elicit both humoral and cellular immunity. CD8+cytotoxic T lymphocytes (CTLs) are directed predominantly against conserved internal proteins and confer cross-protection, even against influenza A viruses of various subtypes. In some CTL epitopes, mutations occur that allow influenza A viruses to evade recognition by CTLs. However, the immunodominant HLA-A*0201-restricted M158–66epitope does not tolerate mutations without loss of viral fitness. Here, we describe naturally occurring variations in amino acid residues outside the M158–66epitope that influence the recognition of the epitope. These results provide novel insights into the epidemiology of influenza A viruses and their pathogenicity and may aid rational design of vaccines that aim at the induction of CTL responses.

scholarly journals In Vitro and In Vivo Antiviral Activity of Gingerenone A on Influenza A Virus Is Mediated by Targeting Janus Kinase 2

Viruses ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 1141
Author(s):  
Jiongjiong Wang ◽  
Richard A. Prinz ◽  
Xiufan Liu ◽  
Xiulong Xu
Keyword(s):  
Antiviral Activity ◽  
Influenza A Virus ◽  
Influenza A ◽  
H5n1 Virus ◽  
Immune Cell ◽  
Janus Kinase ◽  
Virus Infections ◽  
Dual Inhibitor ◽  
Cell Functions

Janus kinase (JAK) inhibitors have been developed as novel immunomodulatory drugs and primarily used for treating rheumatoid arthritis and other inflammatory diseases. Recent studies have suggested that this category of anti-inflammatory drugs could be potentially useful for the control of inflammation “storms” in respiratory virus infections. In addition to their role in regulating immune cell functions, JAK1 and JAK2 have been recently identified as crucial cellular factors involved in influenza A virus (IAV) replication and could be potentially targeted for antiviral therapy. Gingerenone A (Gin A) is a compound derived from ginger roots and a dual inhibitor of JAK2 and p70 S6 kinase (S6K1). Our present study aimed to determine the antiviral activity of Gin A on influenza A virus (IAV) and to understand its mechanisms of action. Here, we reported that Gin A suppressed the replication of three IAV subtypes (H1N1, H5N1, H9N2) in four cell lines. IAV replication was also inhibited by Ruxolitinib (Rux), a JAK inhibitor, but not by PF-4708671, an S6K1 inhibitor. JAK2 overexpression enhanced H5N1 virus replication and attenuated Gin A-mediated antiviral activity. In vivo experiments revealed that Gin A treatment suppressed IAV replication in the lungs of H5N1 virus-infected mice, alleviated their body weight loss, and prolonged their survival. Our study suggests that Gin A restricts IAV replication by inhibiting JAK2 activity; Gin A could be potentially useful for the control of influenza virus infections.

scholarly journals Tbx21 and Foxp3 Are Epigenetically Stabilized in T-Bet+ Tregs That Transiently Accumulate in Influenza A Virus-Infected Lungs

2021 ◽  
Vol 22 (14) ◽  
pp. 7522
Author(s):  
Yassin Elfaki ◽  
Juhao Yang ◽  
Julia Boehme ◽  
Kristin Schultz ◽  
Dunja Bruder ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Influenza A Virus ◽  
Influenza A ◽  
T Cell Subsets ◽  
T Helper 1 ◽  
T Box ◽  
Cell Responses ◽  
Accumulation Kinetics ◽  
Kinetics Of

During influenza A virus (IAV) infections, CD4+ T cell responses within infected lungs mainly involve T helper 1 (Th1) and regulatory T cells (Tregs). Th1-mediated responses favor the co-expression of T-box transcription factor 21 (T-bet) in Foxp3+ Tregs, enabling the efficient Treg control of Th1 responses in infected tissues. So far, the exact accumulation kinetics of T cell subsets in the lungs and lung-draining lymph nodes (dLN) of IAV-infected mice is incompletely understood, and the epigenetic signature of Tregs accumulating in infected lungs has not been investigated. Here, we report that the total T cell and the two-step Treg accumulation in IAV-infected lungs is transient, whereas the change in the ratio of CD4+ to CD8+ T cells is more durable. Within lungs, the frequency of Tregs co-expressing T-bet is steadily, yet transiently, increasing with a peak at Day 7 post-infection. Interestingly, T-bet+ Tregs accumulating in IAV-infected lungs displayed a strongly demethylated Tbx21 locus, similarly as in T-bet+ conventional T cells, and a fully demethylated Treg-specific demethylated region (TSDR) within the Foxp3 locus. In summary, our data suggest that T-bet+ but not T-bet− Tregs are epigenetically stabilized during IAV-induced infection in the lung.

scholarly journals Impact of obesity and SARS-CoV-2 infection: implications for host defence - a living review

2021 ◽  
Vol 2 (1) ◽  
Author(s):  
Felix Clemens Richter ◽  
Aljawharah Alrubayyi ◽  
Alicia Teijeira Crespo ◽  
Sarah Hulin-Curtis ◽  
Keyword(s):  
Lipid Metabolism ◽  
Influenza A ◽  
Immune Cell ◽  
Cell Metabolism ◽  
Low Grade ◽  
Obese Patients ◽  
Healthy Weight ◽  
Virus Infections ◽  
Immune Alterations ◽  
And Function

Abstract The role of obesity in the pathophysiology of respiratory virus infections has become particularly apparent during the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, where obese patients are twice as likely to suffer from severe coronavirus disease 2019 (COVID-19) than healthy weight individuals. Obesity results in disruption of systemic lipid metabolism promoting a state of chronic low-grade inflammation. However, it remains unclear how these underlying metabolic and cellular processes promote severe SARS-CoV-2 infection. Emerging data in SARS-CoV-2 and Influenza A virus (IAV) infections show that viruses can further subvert the host’s altered lipid metabolism and exploit obesity-induced alterations in immune cell metabolism and function to promote chronic inflammation and viral propagation. In this review, we outline the systemic metabolic and immune alterations underlying obesity and discuss how these baseline alterations impact the immune response and disease pathophysiology. A better understanding of the immunometabolic landscape of obese patients may aid better therapies and future vaccine design.

scholarly journals Salidroside Protects Against Influenza A Virus-Induced Acute Lung Injury in Mice

Dose-Response ◽  
2021 ◽  
Vol 19 (2) ◽  
pp. 155932582110113
Author(s):  
Rufeng Lu ◽  
Yueguo Wu ◽  
Honggang Guo ◽  
Zhuoyi Zhang ◽  
Yuzhou He
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Influenza A Virus ◽  
Influenza A ◽  
H1n1 Virus ◽  
Antiviral Agents ◽  
Toll Like Receptor ◽  
Virus Infections ◽  
Toll Like Receptor 4 ◽  
Inflammatory Cytokine Production

Influenza A virus infections can cause acute lung injury (ALI) in humans; thus, the identification of potent antiviral agents is urgently required. Herein, the effects of salidroside on influenza A virus-induced ALI were investigated in a murine model. BALB/c mice were intranasally inoculated with H1N1 virus and treated with salidroside. The results of this study show that salidroside treatment (30 and 60 mg/kg) significantly attenuated the H1N1 virus-induced histological alterations in the lung and inhibited inflammatory cytokine production. Salidroside also decreased the wet/dry ratio, viral titers, and Toll-like receptor 4 expression in the lungs. Therefore, salidroside may represent a potential therapeutic reagent for the treatment of influenza A virus-induced ALI.

scholarly journals Characterization of a Human H5N1 Influenza A Virus Isolated in 2003

2005 ◽  
Vol 79 (15) ◽  
pp. 9926-9932 ◽  
Author(s):  
Kyoko Shinya ◽  
Masato Hatta ◽  
Shinya Yamada ◽  
Ayato Takada ◽  
Shinji Watanabe ◽  
...  
Keyword(s):  
Hong Kong ◽  
Avian Influenza ◽  
Influenza A Virus ◽  
Influenza A ◽  
Mainland China ◽  
Virus Infections ◽  
Influenza A Viruses ◽  
H5n1 Avian Influenza Virus ◽  
H5n1 Influenza ◽  
Avian Influenza A Virus

ABSTRACT In 2003, H5N1 avian influenza virus infections were diagnosed in two Hong Kong residents who had visited the Fujian province in mainland China, affording us the opportunity to characterize one of the viral isolates, A/Hong Kong/213/03 (HK213; H5N1). In contrast to H5N1 viruses isolated from humans during the 1997 outbreak in Hong Kong, HK213 retained several features of aquatic bird viruses, including the lack of a deletion in the neuraminidase stalk and the absence of additional oligosaccharide chains at the globular head of the hemagglutinin molecule. It demonstrated weak pathogenicity in mice and ferrets but caused lethal infection in chickens. The original isolate failed to produce disease in ducks but became more pathogenic after five passages. Taken together, these findings portray the HK213 isolate as an aquatic avian influenza A virus without the molecular changes associated with the replication of H5N1 avian viruses in land-based poultry such as chickens. This case challenges the view that adaptation to land-based poultry is a prerequisite for the replication of aquatic avian influenza A viruses in humans.

The role of host cell Rab GTPases in influenza A virus infections

2021 ◽  
Author(s):  
Jing Wu ◽  
Jiaqi Gu ◽  
Li Shen ◽  
Xiaonan Jia ◽  
Yiqian Yin ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Respiratory Infections ◽  
Small Gtpase ◽  
Regulatory Mechanisms ◽  
Rab Proteins ◽  
Rab Gtpases ◽  
Virus Infections ◽  
Adaptation Mechanisms

Influenza A virus (IAV) is a crucial cause of respiratory infections in humans worldwide. Therefore, studies should clarify adaptation mechanisms of IAV and critical factors of the viral pathogenesis in human hosts. GTPases of the Rab family are the largest branch of the Ras-like small GTPase superfamily, and they regulate almost every step during vesicle-mediated trafficking. Evidence has shown that Rab proteins participate in the lifecycle of IAV. In this mini-review, we outline the regulatory mechanisms of different Rab proteins in the lifecycle of IAV. Understanding the role of Rab proteins in IAV infections is important to develop broad-spectrum host-targeted antiviral strategies.

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