scholarly journals Syrian hamster as an animal model for the study of human influenza virus infection

2017 ◽  
pp. JVI.01693-17 ◽  
Author(s):  
Kiyoko Iwatsuki-Horimoto ◽  
Noriko Nakajima ◽  
Yurie Ichiko ◽  
Yuko Sakai-Tagawa ◽  
Takeshi Noda ◽  
...  
Keyword(s):  
Animal Model ◽  
Virus Infection ◽  
H1n1 Virus ◽  
Influenza Virus Infection ◽  
Small Animal ◽  
Influenza Viruses ◽  
Human Influenza ◽  
Small Animal Model ◽  
Syrian Hamsters ◽  
B Virus

Ferrets and mice are frequently used as animal models for influenza research. However, ferrets are demanding in terms of housing space and handling, whereas mice are not naturally susceptible to infection with human influenza A or B viruses. Therefore, prior adaptation of human viruses is required for their use in mice. In addition, there are no mouse-adapted variants of the recent H3N2 viruses, because these viruses do not replicate well in mice. In this study, we investigated the susceptibility of Syrian hamsters to influenza viruses with a view to using them as an alternative animal model to mice. We found that hamsters are sensitive to influenza viruses, including the recent H3N2 viruses, without adaptation. Although the hamsters did not show weight loss or clinical signs of H3N2 virus infection, we observed pathogenic effects in the respiratory tracts of the infected animals. All of the H3N2 viruses tested replicated in the respiratory organs of the hamsters, and some of them were detected in the nasal washes of infected animals. Moreover, a pdm09 and a seasonal H1N1 virus, as well as one of the two H3N2 viruses, but not a type B virus, were airborne transmissible in these hamsters. Hamsters thus have potential as a small animal model for the study of influenza virus infection, including studies of the pathogenicity of H3N2 viruses and other strains, as well as H1N1 virus transmission studies.IMPORTANCEWe found that Syrian hamsters are susceptible to human influenza viruses, including the recent H3N2 viruses, without adaptation. We also found that a pdm09 and a seasonal H1N1 virus, as well as one of the H3N2 viruses, but not a type B virus tested are airborne transmitted in these hamsters. Syrian hamsters thus have potential as a small animal model for the study of human influenza viruses.

scholarly journals Next Generation of Computationally Optimized Broadly Reactive HA Vaccines Elicited Cross-Reactive Immune Responses and Provided Protection against H1N1 Virus Infection

Vaccines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 793
Author(s):  
Ying Huang ◽  
Monique S. França ◽  
James D. Allen ◽  
Hua Shi ◽  
Ted M. Ross
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Immune Responses ◽  
H1n1 Virus ◽  
Influenza Virus Infection ◽  
H1n1 Influenza ◽  
Influenza Viruses ◽  
Next Generation ◽  
Wild Type ◽  
Influenza A H1n1

Vaccination is the best way to prevent influenza virus infections, but the diversity of antigenically distinct isolates is a persistent challenge for vaccine development. In order to conquer the antigenic variability and improve influenza virus vaccine efficacy, our research group has developed computationally optimized broadly reactive antigens (COBRAs) in the form of recombinant hemagglutinins (rHAs) to elicit broader immune responses. However, previous COBRA H1N1 vaccines do not elicit immune responses that neutralize H1N1 virus strains in circulation during the recent years. In order to update our COBRA vaccine, two new candidate COBRA HA vaccines, Y2 and Y4, were generated using a new seasonal-based COBRA methodology derived from H1N1 isolates that circulated during 2013–2019. In this study, the effectiveness of COBRA Y2 and Y4 vaccines were evaluated in mice, and the elicited immune responses were compared to those generated by historical H1 COBRA HA and wild-type H1N1 HA vaccines. Mice vaccinated with the next generation COBRA HA vaccines effectively protected against morbidity and mortality after infection with H1N1 influenza viruses. The antibodies elicited by the COBRA HA vaccines were highly cross-reactive with influenza A (H1N1) pdm09-like viruses isolated from 2009 to 2021, especially with the most recent circulating viruses from 2019 to 2021. Furthermore, viral loads in lungs of mice vaccinated with Y2 and Y4 were dramatically reduced to low or undetectable levels, resulting in minimal lung injury compared to wild-type HA vaccines following H1N1 influenza virus infection.

scholarly journals Tropism and Infectivity of a Seasonal A(H1N1) and a Highly Pathogenic Avian A(H5N1) Influenza Virus in Primary Differentiated Ferret Nasal Epithelial Cell Cultures

2019 ◽  
Vol 93 (10) ◽  
Author(s):  
Hui Zeng ◽  
Cynthia S. Goldsmith ◽  
Amrita Kumar ◽  
Jessica A. Belser ◽  
Xiangjie Sun ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Avian Influenza ◽  
H5n1 Virus ◽  
H1n1 Virus ◽  
Influenza Virus Infection ◽  
Influenza Viruses ◽  
Host Interactions ◽  
Culture Model

ABSTRACTFerrets represent an invaluable animal model to study influenza virus pathogenesis and transmission. To further characterize this model, we developed a differentiated primary ferret nasal epithelial cell (FNEC) culture model for investigation of influenza A virus infection and virus-host interactions. This well-differentiated culture consists of various cell types, a mucociliary clearance system, and tight junctions, representing the nasal ciliated pseudostratified respiratory epithelium. Both α2,6-linked and α2,3-linked sialic acid (SA) receptors, which preferentially bind the hemagglutinin (HA) of human and avian influenza viruses, respectively, were detected on the apical surface of the culture with different cellular tropisms. In accordance with the distribution of SA receptors, we observed that a pre-2009 seasonal A(H1N1) virus infected both ciliated and nonciliated cells, whereas a highly pathogenic avian influenza (HPAI) A(H5N1) virus primarily infected nonciliated cells. Transmission electron microscopy revealed that virions were released from or associated with the apical membranes of ciliated, nonciliated, and mucin-secretory goblet cells. Upon infection, the HPAI A(H5N1) virus replicated to titers higher than those of the human A(H1N1) virus at 37°C; however, replication of the A(H5N1) virus was significantly attenuated at 33°C. Furthermore, we found that infection with the A(H5N1) virus induced higher expression levels of immune mediator genes and resulted in more cell damage/loss than with the human A(H1N1) virus. This primary differentiated FNEC culture model, recapitulating the structure of the nasal epithelium, provides a useful model to bridgein vivoandin vitrostudies of cellular tropism, infectivity, and pathogenesis of influenza viruses during the initial stages of infection.IMPORTANCEAlthough ferrets serve as an important model of influenza virus infection, much remains unknown about virus-host interactions in this species at the cellular level. The development of differentiated primary cultures of ferret nasal epithelial cells is an important step toward understanding cellular tropism and the mechanisms of influenza virus infection and replication in the airway milieu of this model. Using lectin staining and microscopy techniques, we characterized the sialic acid receptor distribution and the cellular composition of the culture model. We then evaluated the replication of and immune response to human and avian influenza viruses at relevant physiological temperatures. Our findings offer significant insight into this first line of defense against influenza virus infection and provide a model for the evaluation of emerging influenza viruses in a well-controlledin vitroenvironmental setting.

scholarly journals Constitutively Expressed IFITM3 Protein in Human Endothelial Cells Poses an Early Infection Block to Human Influenza Viruses

2016 ◽  
Vol 90 (24) ◽  
pp. 11157-11167 ◽  
Author(s):  
Xiangjie Sun ◽  
Hui Zeng ◽  
Amrita Kumar ◽  
Jessica A. Belser ◽  
Taronna R. Maines ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Influenza Virus ◽  
Virus Infection ◽  
Avian Influenza ◽  
Influenza Virus Infection ◽  
Influenza Viruses ◽  
Human Influenza ◽  
Avian Influenza Viruses ◽  
Human Influenza Virus ◽  
Pulmonary Endothelial Cells

ABSTRACTA role for pulmonary endothelial cells in the orchestration of cytokine production and leukocyte recruitment during influenza virus infection, leading to severe lung damage, has been recently identified. As the mechanistic pathway for this ability is not fully known, we extended previous studies on influenza virus tropism in cultured human pulmonary endothelial cells. We found that a subset of avian influenza viruses, including potentially pandemic H5N1, H7N9, and H9N2 viruses, could infect human pulmonary endothelial cells (HULEC) with high efficiency compared to human H1N1 or H3N2 viruses. In HULEC, human influenza viruses were capable of binding to host cellular receptors, becoming internalized and initiating hemifusion but failing to uncoat the viral nucleocapsid and to replicate in host nuclei. Unlike numerous cell types, including epithelial cells, we found that pulmonary endothelial cells constitutively express a high level of the restriction protein IFITM3 in endosomal compartments. IFITM3 knockdown by small interfering RNA (siRNA) could partially rescue H1N1 virus infection in HULEC, suggesting IFITM3 proteins were involved in blocking human influenza virus infection in endothelial cells. In contrast, selected avian influenza viruses were able to escape IFITM3 restriction in endothelial cells, possibly by fusing in early endosomes at higher pH or by other, unknown mechanisms. Collectively, our study demonstrates that the human pulmonary endothelium possesses intrinsic immunity to human influenza viruses, in part due to the constitutive expression of IFITM3 proteins. Notably, certain avian influenza viruses have evolved to escape this restriction, possibly contributing to virus-induced pneumonia and severe lung disease in humans.IMPORTANCEAvian influenza viruses, including H5N1 and H7N9, have been associated with severe respiratory disease and fatal outcomes in humans. Although acute respiratory distress syndrome (ARDS) and progressive pulmonary endothelial damage are known to be present during severe human infections, the role of pulmonary endothelial cells in the pathogenesis of avian influenza virus infections is largely unknown. By comparing human seasonal influenza strains to avian influenza viruses, we provide greater insight into the interaction of influenza virus with human pulmonary endothelial cells. We show that human influenza virus infection is blocked during the early stages of virus entry, which is likely due to the relatively high expression of the host antiviral factors IFITMs (interferon-induced transmembrane proteins) located in membrane-bound compartments inside cells. Overall, this study provides a mechanism by which human endothelial cells limit replication of human influenza virus strains, whereas avian influenza viruses overcome these restriction factors in this cell type.

scholarly journals Host DNA released by NETosis in neutrophils exposed to seasonal H1N1 and highly pathogenic H5N1 influenza viruses

2020 ◽  
Author(s):  
Louisa L.Y. Chan ◽  
John M. Nicholls ◽  
J.S. Malik Peiris ◽  
Yu Lung Lau ◽  
Michael C.W. Chan ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
H1n1 Virus ◽  
Influenza Virus Infection ◽  
Alveolar Epithelium ◽  
Influenza Viruses ◽  
H5n1 Influenza Virus ◽  
H5n1 Influenza ◽  
Influenza H1n1

Abstract Background Neutrophil (Nϕ) is of the most abundant number in human immune system. During acute influenza virus infection, Nϕs are already active in the early phase of inflammation-a time in which clinical biopsy or autopsy material is not readily available. However, the role of Nϕ in virus infection is not well understood. Here, we studied the role of Nϕ in host defense during influenza A virus infection, specifically assessing if it contributes to the differential pathogenesis in H5N1 disease. Methods Nϕs were freshly isolated from healthy volunteers and subjected to direct influenza H1N1 and H5N1 virus infection in vitro . The ability of the naïve Nϕs to infiltrate from the basolateral to the apical phase of the influenza virus infected alveolar epithelium was assessed. The viral replication, innate immune responses and Neutrophil extracellular trap (NET) formation of Nϕs upon influenza virus infection were evaluated. Results Our results demonstrated that influenza virus infected alveolar epithelium allowed more Nϕs transmigration. Significantly more Nϕs migrated across the H5N1 influenza virus infected the epithelium than the counterpart infected by the seasonal influenza H1N1 virus infected. Nϕs were equally susceptible to H5N1 and H1N1 virus infection with similar viral gene transcription. Productive replication was observed in H5N1 infected Nϕs. Both H5N1 and H1N1 infected Nϕs induced cytokines and chemokines including TNF-α, IFN-β, CXCL10, MIP-1α and IL-8. This inferred a more intense inflammatory response posed by H5N1 than H1N1 virus. Strikingly, NADPH oxidase-independent NET formation was observed in H1N1 infected Nϕs at 6 hpi while no NET formation was observed upon H5N1 infection. Conclusion Our data is the first to demonstrate that NET formation is abrogated in H5N1 influenza virus infection. Its contribution to the differential severity of H5N1 disease requires further investigation.

scholarly journals Long-Acting Neuraminidase Inhibitor Laninamivir Octanoate (CS-8958) versus Oseltamivir as Treatment for Children with Influenza Virus Infection

2010 ◽  
Vol 54 (6) ◽  
pp. 2575-2582 ◽  
Author(s):  
Norio Sugaya ◽  
Yasuo Ohashi
Keyword(s):  
Virus Infection ◽  
Influenza A ◽  
H1n1 Virus ◽  
Controlled Trial ◽  
Influenza Virus Infection ◽  
Neuraminidase Inhibitor ◽  
Double Blind ◽  
Influenza A H1n1 ◽  
B Virus ◽  
Long Acting

ABSTRACT We conducted a double-blind, randomized controlled trial to compare a long-acting neuraminidase inhibitor, laninamivir octanoate, with oseltamivir. Eligible patients were children 9 years of age and under who had febrile influenza symptoms of no more than 36-h duration. Patients were randomized to 1 of 3 treatment groups: a group given 40 mg laninamivir (40-mg group), a group given 20 mg laninamivir (20-mg group), and an oseltamivir group. Laninamivir octanoate was administered as a single inhalation. Oseltamivir (2 mg/kg of body weight) was administered orally twice daily for 5 days. The primary end point was the time to alleviation of influenza illness. The primary analysis included 184 patients (61, 61, and 62 in the 40-mg group, 20-mg group, and oseltamivir group, respectively). Laninamivir octanoate markedly reduced the median time to illness alleviation in comparison with oseltamivir in patients infected with oseltamivir-resistant influenza A (H1N1) virus, and the reductions were 60.9 h for the 40-mg group and 66.2 h for the 20-mg group. On the other hand, there were no significant differences in the times to alleviation of illness between the laninamivir groups and oseltamivir group for patients with influenza A (H3N2) or B virus infection. Laninamivir octanoate was well tolerated. The most common adverse events were gastrointestinal events. Laninamivir octanoate was an effective and well-tolerated treatment for children with oseltamivir-resistant influenza A (H1N1) virus infection. Further study will be needed to confirm clinical efficacy against influenza A (H3N2) or B virus infection. Its ease of administration is noteworthy, because a single inhalation is required during the course of illness.

Tissue distribution of human and avian type sialic acid influenza virus receptors in domestic cat

2013 ◽  
Vol 61 (4) ◽  
pp. 537-546 ◽  
Author(s):  
Heng Wang ◽  
Xintao Wu ◽  
Yanfen Cheng ◽  
Yufu An ◽  
Zhangyong Ning
Keyword(s):  
Influenza Virus ◽  
Sialic Acid ◽  
Gastrointestinal Tract ◽  
Virus Infection ◽  
Tissue Distribution ◽  
Influenza Virus Infection ◽  
Influenza Viruses ◽  
Domestic Cat ◽  
Host Cells ◽  
Human Influenza

Infection of host cells with the influenza virus is mediated by specific interactions between the viral haemagglutinin (HA) and cell oligosaccharides containing sialic acid (SA) residues. Avian and human influenza viruses bind to alpha-2, 3 and alpha-2, 6 sialic acid-linked receptors, respectively. To date, there have been no detailed tissue distribution data on alpha-2, 3 and alpha-2, 6 sialic acid-linked receptors in the domestic cat, a relatively new mammalian host for influenza virus infections. In this study, the tissue distribution of human and avian type sialic acid influenza receptors was determined in various organs (respiratory tract, gastrointestinal tract, brain, cerebellum, spleen, kidney, heart and pancreas) of domestic cat by binding with the lectinsMaackia amurensisagglutinin II (MAA II) andSambucus nigraagglutinin (SNA), respectively. The results revealed that both alpha-2, 3 and alpha-2, 6 sialic acid-linked receptors were extensively detected in the trachea, bronchus, lung, kidney, spleen, pancreas and gastrointestinal tract. Endothelial cells of gastrointestinal tract organs were negative for alpha-2, 3 sialic acid-linked receptors in cats. The presence of alpha-2, 3 and alpha-2, 6 sialic acid-linked receptors in the major organs examined in the present study suggests that each major organ may be affected by influenza virus infection. Because of receptor distribution in the gastrointestinal tract, the experimental infection of cats with human influenza virus may be relatively easy while their infection with avian influenza virus may be difficult. These data can explain the involvement of multiple organs in influenza virus infection and should help investigators interpret the results obtained when cats are infected with influenza virus and estimate the risk of infection between cats and humans.

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