Influenza virus and SARS-CoV-2: pathogenesis and host responses in the respiratory tract

Central nervous system (CNS) disease is one of the most common extra-respiratory tract complications of influenza A virus (IAV) infections. However, there is still little knowledge about IAV regulating host responses in brain.

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A Live-Attenuated Prime, Inactivated Boost Vaccination Strategy with Chimeric Hemagglutinin-Based Universal Influenza Virus Vaccines Provides Protection in Ferrets: A Confirmatory Study

Vaccines ◽

10.3390/vaccines6030047 ◽

2018 ◽

Vol 6 (3) ◽

pp. 47 ◽

Cited By ~ 15

Author(s):

Raffael Nachbagauer ◽

Florian Krammer ◽

Randy Albrecht

Keyword(s):

Influenza Virus ◽

Respiratory Tract ◽

Virus Vaccine ◽

Influenza Viruses ◽

Inactivated Vaccine ◽

Upper Respiratory Tract ◽

Live Attenuated Vaccine ◽

Virus Surface ◽

Virus Challenge ◽

Attenuated Vaccine

Influenza viruses cause severe diseases and mortality in humans on an annual basis. The current influenza virus vaccines can confer protection when they are well-matched with the circulating strains. However, due to constant changes of the virus surface glycoproteins, the vaccine efficacy can drop substantially in some seasons. In addition, the current seasonal influenza virus vaccines do not protect from avian influenza viruses of human pandemic potential. Novel influenza virus vaccines that aim to elicit antibodies against conserved epitopes like the hemagglutinin stalk could not only reduce the burden of drifted seasonal viruses but potentially also protect humans from infection with zoonotic and emerging pandemic influenza viruses. In this paper, we generated influenza virus vaccine constructs that express chimeric hemagglutinins consisting of exotic, avian head domains and a consistent stalk domain of a seasonal virus. Using such viruses in a sequential immunization regimen can redirect the immune response towards conserved epitopes. In this study, male ferrets received a live-attenuated vaccine virus based on the A/Ann Arbor/6/60 strain expressing a chimeric H8/1 (cH8/1) hemagglutinin, which was followed by a heterologous booster vaccination with a cH5/1N1 formalin inactivated non-adjuvanted whole virus. This group was compared to a second group that received a cH8/1N1 inactivated vaccine followed by a cH5/1N1 inactivated vaccine. Both groups showed a reduction in viral titers in the upper respiratory tract after the A(H1N1)pdm09 virus challenge. Animals that received the live-attenuated vaccine had low or undetectable titers in the lower respiratory tract. The results support the further development of chimeric hemagglutinin-based vaccination strategies. The outcome of this study confirms and corroborates findings from female ferrets primed with a A/Leningrad/134/17/57-based live attenuated cH8/1N1 vaccine followed by vaccination with an AS03-adjuvanted cH5/1N1 split virus vaccine 10.

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Replication and Transmission of the Novel Bovine Influenza D Virus in a Guinea Pig Model

Journal of Virology ◽

10.1128/jvi.01630-15 ◽

2015 ◽

Vol 89 (23) ◽

pp. 11990-12001 ◽

Cited By ~ 40

Author(s):

Chithra Sreenivasan ◽

Milton Thomas ◽

Zizhang Sheng ◽

Ben M. Hause ◽

Emily A. Collin ◽

...

Keyword(s):

Influenza Virus ◽

Respiratory Tract ◽

Guinea Pigs ◽

Clinical Signs ◽

Suitable Model ◽

Upper Respiratory Tract ◽

Experimental Conditions ◽

Primary Host ◽

Transmission Potential ◽

Sentinel Animals

ABSTRACTInfluenza D virus (FLUDV) is a novel influenza virus that infects cattle and swine. The goal of this study was to investigate the replication and transmission of bovine FLUDV in guinea pigs. Following direct intranasal inoculation of animals, the virus was detected in nasal washes of infected animals during the first 7 days postinfection. High viral titers were obtained from nasal turbinates and lung tissues of directly inoculated animals. Further, bovine FLUDV was able to transmit from the infected guinea pigs to sentinel animals by means of contact and not by aerosol dissemination under the experimental conditions tested in this study. Despite exhibiting no clinical signs, infected guinea pigs developed seroconversion and the viral antigen was detected in lungs of animals by immunohistochemistry. The observation that bovine FLUDV replicated in the respiratory tract of guinea pigs was similar to observations described previously in studies of gnotobiotic calves and pigs experimentally infected with bovine FLUDV but different from those described previously in experimental infections in ferrets and swine with a swine FLUDV, which supported virus replication only in the upper respiratory tract and not in the lower respiratory tract, including lung. Our study established that guinea pigs could be used as an animal model for studying this newly emerging influenza virus.IMPORTANCEInfluenza D virus (FLUDV) is a novel emerging pathogen with bovine as its primary host. The epidemiology and pathogenicity of the virus are not yet known. FLUDV also spreads to swine, and the presence of FLUDV-specific antibodies in humans could indicate that there is a potential for zoonosis. Our results showed that bovine FLUDV replicated in the nasal turbinate and lungs of guinea pigs at high titers and was also able to transmit from an infected animal to sentinel animals by contact. The fact that bovine FLUDV replicated productively in both the upper and lower respiratory tracts of guinea pigs, similarly to virus infection in its native host, demonstrates that guinea pigs would be a suitable model host to study the replication and transmission potential of bovine FLUDV.

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Interleukin 12 is a primary cytokine responding to influenza virus infection in the respiratory tract of mice

Acta Virologica ◽

10.4149/av_2009_04_233 ◽

2009 ◽

Vol 53 (4) ◽

pp. 233-240 ◽

Cited By ~ 14

Author(s):

Y. Hama ◽

M. Kurokawa ◽

M. Imakita ◽

Y. Yoshida ◽

T. Shimizu ◽

...

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

Respiratory Tract ◽

Influenza Virus Infection ◽

Interleukin 12

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Radiologic Findings of Childhood Lower Respiratory Tract Infection by Influenza Virus

Journal of the Korean Radiological Society ◽

10.3348/jkrs.2002.47.2.227 ◽

2002 ◽

Vol 47 (2) ◽

pp. 227 ◽

Cited By ~ 1

Author(s):

Hotaek Song ◽

Choong Ki Park ◽

Hee Jung Shin ◽

Yo Won Choi ◽

Seok Chol Jeon ◽

...

Keyword(s):

Influenza Virus ◽

Tract Infection ◽

Respiratory Tract ◽

Respiratory Tract Infection ◽

Lower Respiratory Tract Infection ◽

Lower Respiratory Tract ◽

Radiologic Findings

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Increased Detection of Viruses in Children with Respiratory Tract Infection Using PCR

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17020564 ◽

2020 ◽

Vol 17 (2) ◽

pp. 564 ◽

Cited By ~ 7

Author(s):

Chien-Yu Lin ◽

David Hwang ◽

Nan-Chang Chiu ◽

Li-Chuan Weng ◽

Hsin-Fu Liu ◽

...

Keyword(s):

Influenza Virus ◽

Tract Infection ◽

Respiratory Tract ◽

Respiratory Tract Infection ◽

Respiratory Viruses ◽

Accurate Diagnosis ◽

Human Bocavirus ◽

Detection Rates ◽

Syncytial Virus ◽

Antigen Tests

Respiratory viruses are a common cause of respiratory tract infection (RTI), particularly in neonates and children. Rapid and accurate diagnosis of viral infections could improve clinical outcomes and reduce the use of antibiotics and treatment sessions. Advances in diagnostic technology contribute to the accurate detection of viruses. We performed a multiplex real-time polymerase chain reaction (PCR) to investigate the viral etiology in pediatric patients and compared the detection rates with those determined using traditional antigen tests and virus cultures. Fifteen respiratory viruses were included in our investigation: respiratory syncytial virus A/B (RSV), influenza virus A (FluA) and influenza virus B (FluB), human metapneumovirus (MPV), enterovirus (EV), human parainfluenza virus (PIV) types 1–4, human rhinovirus (RV), human coronavirus OC43, NL63, and 229E, human adenovirus (ADV), and human bocavirus (Boca). In total, 474 specimens were collected and tested. Respiratory viruses were detected more frequently by PCR (357, 75.3%) than they were by traditional tests (229, 49.3%). The leading pathogens were RSV (113, 23.8%), RV (72, 15.2%), PIV3 (53, 11.2%), FluA (51, 10.8%), and ADV (48, 10.1%). For children younger than 5 years, RSV and RV were most prevalent; for children older than 5 years, FluA and ADV were the most frequently detected. Of the specimens, 25.8% (92/357) were coinfected with two or more viruses. RV, Boca, PIV2, FluB, and PIV4 had higher rates of coinfection; MPV and PIV1 had the lowest rates of coinfection (9.1% and 5.3%). To conclude, the detection power of PCR was better than that of traditional antigen tests and virus cultures when considering the detection of respiratory viruses. RSV and RV were the leading viral pathogens identified in the respiratory specimens. One-quarter of the positive specimens were coinfected with two or more viruses. In the future, further application of PCR may contribute to the rapid and accurate diagnosis of respiratory viruses and could improve patient outcomes.

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Nasal commensal, Staphylococcus epidermidis shapes the mucosal environment to prevent influenza virus invasion through Serpine1 induction

10.1101/2020.08.03.235648 ◽

2020 ◽

Author(s):

Ara Jo ◽

Jina Won ◽

Chan Hee Chil ◽

Jae Young Choi ◽

Kang-Mu Lee ◽

...

Keyword(s):

Influenza Virus ◽

Respiratory Tract ◽

Protease Inhibitor ◽

Serine Protease ◽

Nasal Mucosa ◽

Staphylococcus Epidermidis ◽

Influenza Virus Infection ◽

Serine Protease Inhibitor ◽

Cellular Environment

ABSTRACTOur recent study presented evidence that Staphylococcus epidermidis (S. epidermidis) was the most frequently encountered microbiome component in healthy human nasal mucus and that S. epidermidis could induce interferon (IFN)-dependent innate immunity to control acute viral lung infection. The serine protease inhibitor Serpine1 was identified to inhibit influenza A virus (IAV) spread by inhibiting glycoprotein cleavage, and the current study supports an additional mechanism of Serpine1 induction in the nasal mucosa, which can be regulated through S. epidermidis and IFN signaling. The exposure of in vivo mice to human S. epidermidis increased IFN-λ secretion in nasal mucosa and prevented an increase in the burden of IAV in the lung. S. epidermidis-inoculated mice exhibited the significant induction of Serpine1 in vivo in the nasal mucosa, and by targeting airway protease, S. epidermidis-induced Serpine1 inhibited the intracellular invasion of IAV to the nasal epithelium and led to restriction of IAV spreading to the lung. Furthermore, IFN-λ secretion was involved in the regulation of Serpine1 in S. epidermidis-inoculated nasal epithelial cells and in vivo nasal mucosa, and this was biologically relevant for the role of Serpine1 as an interferon-stimulated gene in the upper airway. Together, our findings reveal that human nasal commensal S. epidermidis manipulates the suppression of serine protease in in vivo nasal mucosa through Serpine1 induction and protects the nasal mucosa from IAV invasion through IFN-λ signaling.IMPORTANCEPreviously, we proved that nasal microbiome could enhance IFN-related innate immune responses to protect the respiratory tract against influenza virus infection. The present study shows a great understanding of the intimate association of S. epidermidis-regulated IFN-lambda induction and serine protease inhibitor in nasal mucosa. Our data demonstrate that S. epidermidis-regulated Serpine1 suppresses the invasion of influenza virus through suppression of airway serine protease at the level of nasal mucosa and impedes IAV spread to the respiratory tract. Thus, human nasal commensal S. epidermidis represents a therapeutic potential for treating respiratory viral infections via the change of cellular environment in respiratory tract.

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Chronic Heat Stress Weakened the Innate Immunity and Increased the Virulence of Highly Pathogenic Avian Influenza Virus H5N1 in Mice

Journal of Biomedicine and Biotechnology ◽

10.1155/2011/367846 ◽

2011 ◽

Vol 2011 ◽

pp. 1-10 ◽

Cited By ~ 26

Author(s):

Yi Jin ◽

Yanxin Hu ◽

Deping Han ◽

Ming Wang

Keyword(s):

Innate Immunity ◽

Influenza Virus ◽

Heat Stress ◽

Avian Influenza ◽

Respiratory Tract ◽

Avian Influenza Virus ◽

Mrna Levels ◽

Local Immunity ◽

Virus H5n1 ◽

Avian Influenza Virus H5n1

Chronic heat stress (CHS) can negatively affect immune response in animals. In this study we assessed the effects of CHS on host innate immunity and avian influenza virus H5N1 infection in mice. Mice were divided into two groups: CHS and thermally neutral (TN). The CHS treatment group exhibited reduced local immunity in the respiratory tract, including the number of pulmonary alveolar macrophages and lesions in the nasal mucosa, trachea, and lungs. Meanwhile, CHS retarded dendritic cells (DCs) maturation and reduced the mRNA levels of IL-6 and IFN-βsignificantly (P<.05). After the CHS treatment, mice were infected with H5N1 virus. The mortality rate and viral load in the lungs of CHS group were higher than those of TN group. The results suggest that the CHS treatment could suppress local immunity in the respiratory tract and innate host immunity in mice significantly and moderately increased the virulence in H5N1-infected mice.

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The NS Segment of H1N1pdm09 Enhances H5N1 Pathogenicity in a Mouse Model of Influenza Virus Infections

Viruses ◽

10.3390/v10090504 ◽

2018 ◽

Vol 10 (9) ◽

pp. 504

Author(s):

Olivier Ferraris ◽

Jean-Sébastien Casalegno ◽

Emilie Frobert ◽

Maude Bouscambert Duchamp ◽

Martine Valette ◽

...

Keyword(s):

Influenza Virus ◽

Respiratory Tract ◽

Lower Respiratory Tract ◽

Target Cells ◽

Virus Infections ◽

Reassortment Event ◽

Highly Pathogenic ◽

2009 H1n1 ◽

Reassortant Viruses

In 2009, the co-circulation of H5N1 and H1N1pdm09 raised concerns that a reassortment event may lead to highly pathogenic influenza strains. H1N1pdm09 and H5N1 are able to infect the same target cells of the lower respiratory tract. To investigate the capacity of the emergence of reassortant viruses, we characterized viruses obtained from the co-infection of cells with H5N1 (A/Turkey/13/2006) and H1N1pdm09 (A/Lyon/969/2009 H1N1). In our analysis, all the screened reassortants possessed the PB2, HA, and NP segments from H5N1 and acquired one or two of the H1N1pdm09 segments. Moreover, the in vivo infections showed that the acquisition of the NS segment from H1N1pdm09 increased the virulence of H5N1 in mice. We conclude, therefore, that reassortment can occur between these two viruses, even if this process has never been detected in nature.

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The Flu and Richard Pfeiffer

Continual Raving ◽

10.1093/oso/9780190677312.003.0002 ◽

2019 ◽

pp. 23-56

Author(s):

Janet R. Gilsdorf

Keyword(s):

Influenza Virus ◽

Bacterial Meningitis ◽

Respiratory Tract ◽

Haemophilus Influenzae ◽

Bacterial Infections ◽

Scientific Understanding ◽

Nutritional Requirements ◽

Full Potential ◽

Human Pathogen ◽

Evolutionary Patterns

For decades, scientists puzzled over which influenza virus was actually responsible for the Russian pandemic. Finally, in 2014, phylogenetic techniques (examining evolutionary patterns of the virus genes) and seroarcheologic techniques (measuring antibodies likely present in people at various points in time) were applied to the question of which virus caused the Russian flu of 1889–1892. Thus, Pfeiffer’s proclamation that his bacillus caused influenza was finally proven wrong. His identification of Bacillus influenzae in the respiratory tract, however, was a major contribution to the scientific understanding of bacterial infections and moved the field of bacteriology forward in allowing other investigators to unearth its full potential as an important human pathogen. Further, in the course of his studies of B. influenzae, Pfeiffer pioneered the field of nutritional requirements of bacteria. Finally, Pfeiffer’s identification of Haemophilus influenzae launched subsequent studies of the causes of bacterial meningitis and initiated in-depth explorations of bacterial meningitis-causing pathogens that ground our concepts of pathogenesis, and guide our management, of the infection.

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