Characterization of influenza A virus activation of the human neutrophil

Neutrophil dysfunction consequent to influenza A virus infection has been described in vivo and in vitro and may contribute to the serious bacterial sequelae which occur in influenza-infected hosts. On the premise that such dysfunction may represent a form of “deactivation,” we sought to characterize neutrophil activation by the virus in comparison with other agonists. The virus induces a respiratory burst in which H2O2 (but not O2-) are formed. Preceding the respiratory burst, a rise in intracellular calcium (Ca2+i) is noted, but both responses are nearly independent of extracellular Ca2+, unlike those elicited by the other well-characterized Ca2+-dependent agonists, formyl-methyl-leucyl-phenylalanine (FMLP), or Concanavalin-A (Con-A). The Ca2+ increase is paralleled by IP3 generation, implying that it is the result of phospholipase C (PLC) activation. The virus also elicits neutrophil membrane depolarization, which is independently mediated from the Ca2+ increase and respiratory burst and may reflect protein kinase C (PK-C) activation. Virus-induced responses are insensitive to pertussis toxin (PT); cholera toxin does inhibit these responses but in a nonspecific manner. Thus, although influenza virus activates PLC in neutrophils, it does so in a PT-insensitive manner and does not elicit or require a discernible Ca2+ influx to generate a respiratory burst response. In aggregate, the data indicate that influenza A virus activates neutrophils in a manner distinct from that of other well- described neutrophil agonists. These results illustrate the diversity of neutrophil activation mechanisms and support the notion that further characterization of this pathway may facilitate understanding of neutrophil dysfunction induced by the virus.

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Characterization of influenza A virus activation of the human neutrophil

Blood ◽

10.1182/blood.v75.1.218.218 ◽

1990 ◽

Vol 75 (1) ◽

pp. 218-226 ◽

Cited By ~ 33

Author(s):

KL Hartshorn ◽

M Collamer ◽

MR White ◽

JH Schwartz ◽

AI Tauber

Keyword(s):

Influenza A Virus ◽

Respiratory Burst ◽

Influenza A ◽

Neutrophil Activation ◽

Kinase C ◽

Activation Mechanisms ◽

Neutrophil Dysfunction

Abstract Neutrophil dysfunction consequent to influenza A virus infection has been described in vivo and in vitro and may contribute to the serious bacterial sequelae which occur in influenza-infected hosts. On the premise that such dysfunction may represent a form of “deactivation,” we sought to characterize neutrophil activation by the virus in comparison with other agonists. The virus induces a respiratory burst in which H2O2 (but not O2-) are formed. Preceding the respiratory burst, a rise in intracellular calcium (Ca2+i) is noted, but both responses are nearly independent of extracellular Ca2+, unlike those elicited by the other well-characterized Ca2+-dependent agonists, formyl-methyl-leucyl-phenylalanine (FMLP), or Concanavalin-A (Con-A). The Ca2+ increase is paralleled by IP3 generation, implying that it is the result of phospholipase C (PLC) activation. The virus also elicits neutrophil membrane depolarization, which is independently mediated from the Ca2+ increase and respiratory burst and may reflect protein kinase C (PK-C) activation. Virus-induced responses are insensitive to pertussis toxin (PT); cholera toxin does inhibit these responses but in a nonspecific manner. Thus, although influenza virus activates PLC in neutrophils, it does so in a PT-insensitive manner and does not elicit or require a discernible Ca2+ influx to generate a respiratory burst response. In aggregate, the data indicate that influenza A virus activates neutrophils in a manner distinct from that of other well- described neutrophil agonists. These results illustrate the diversity of neutrophil activation mechanisms and support the notion that further characterization of this pathway may facilitate understanding of neutrophil dysfunction induced by the virus.

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Respiratory innate immune proteins differentially modulate the neutrophil respiratory burst response to influenza A virus

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00130.2005 ◽

2005 ◽

Vol 289 (4) ◽

pp. L606-L616 ◽

Cited By ~ 39

Author(s):

Mitchell R. White ◽

Erika Crouch ◽

Jenny Vesona ◽

Paul J. Tacken ◽

Joseph J. Batenburg ◽

...

Keyword(s):

Influenza A Virus ◽

Respiratory Burst ◽

Influenza A ◽

Surfactant Protein ◽

Innate Immune ◽

Proinflammatory Effect ◽

Dose Dependent ◽

Neutrophil Respiratory Burst

Oxidants and neutrophils contribute to lung injury during influenza A virus (IAV) infection. Surfactant protein (SP)-D plays a pivotal role in restricting IAV replication and inflammation in the first several days after infection. Despite its potent anti-inflammatory effects in vivo, preincubation of IAV with SP-D in vitro strongly increases neutrophil respiratory burst responses to the virus. Several factors are shown to modify this apparent proinflammatory effect of SP-D. Although multimeric forms of SP-D show dose-dependent augmentation of respiratory burst responses, trimeric, single-arm forms either show no effect or inhibit these responses. Furthermore, if neutrophils are preincubated with multimeric SP-D before IAV is added, oxidant responses to the virus are significantly reduced. The ability of SP-D to increase neutrophil uptake of IAV can be dissociated from enhancement of oxidant responses. Finally, several other innate immune proteins that bind to SP-D and/or IAV (i.e., SP-A, lung glycoprotein-340 or mucin) significantly reduce the ability of SP-D to promote neutrophil oxidant response. As a result, the net effect of bronchoalveolar lavage fluids is to increase neutrophil uptake of IAV while reducing the respiratory burst response to virus.

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Antiviral activity of Ladania067, an extract from wild black currant leaves against influenza A virus in vitro and in vivo

Frontiers in Microbiology ◽

10.3389/fmicb.2014.00171 ◽

2014 ◽

Vol 5 ◽

Cited By ~ 12

Author(s):

Emanuel Haasbach ◽

Carmen Hartmayer ◽

Alice Hettler ◽

Alicja Sarnecka ◽

Ulrich Wulle ◽

...

Keyword(s):

Antiviral Activity ◽

Influenza A Virus ◽

Influenza A ◽

Black Currant

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Exacerbation of Influenza A Virus Disease Severity by Respiratory Syncytial Virus Co-Infection in a Mouse Model

Viruses ◽

10.3390/v13081630 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1630 ◽

Cited By ~ 1

Author(s):

Junu A. George ◽

Shaikha H. AlShamsi ◽

Maryam H. Alhammadi ◽

Ahmed R. Alsuwaidi

Keyword(s):

T Cells ◽

Respiratory Syncytial Virus ◽

Influenza A Virus ◽

Influenza A ◽

Immune Cell ◽

Virus Disease ◽

Viral Loads ◽

Syncytial Virus

Influenza A virus (IAV) and respiratory syncytial virus (RSV) are leading causes of childhood infections. RSV and influenza are competitive in vitro. In this study, the in vivo effects of RSV and IAV co-infection were investigated. Mice were intranasally inoculated with RSV, with IAV, or with both viruses (RSV+IAV and IAV+RSV) administered sequentially, 24 h apart. On days 3 and 7 post-infection, lung tissues were processed for viral loads and immune cell populations. Lung functions were also evaluated. Mortality was observed only in the IAV+RSV group (50% of mice did not survive beyond 7 days). On day 3, the viral loads in single-infected and co-infected mice were not significantly different. However, on day 7, the IAV titer was much higher in the IAV+RSV group, and the RSV viral load was reduced. CD4 T cells were reduced in all groups on day 7 except in single-infected mice. CD8 T cells were higher in all experimental groups except the RSV-alone group. Increased airway resistance and reduced thoracic compliance were demonstrated in both co-infected groups. This model indicates that, among all the infection types we studied, infection with IAV followed by RSV is associated with the highest IAV viral loads and the most morbidity and mortality.

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The combination of ribavirin and ozeltamivir effectively inhibits reproduction of influenza a virus resistant to rimantadine (Amantadine) in vitro and in vivo

Doklady Biochemistry and Biophysics ◽

10.1134/s1607672914020100 ◽

2014 ◽

Vol 455 (1) ◽

pp. 80-83 ◽

Cited By ~ 3

Author(s):

P. G. Deryabin ◽

G. A. Galegov ◽

I. D. Konstantinova ◽

I. S. Muzyka ◽

A. I. Miroshnikov ◽

...

Keyword(s):

Influenza A Virus ◽

Influenza A

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In vitro and in vivo mechanism of immunomodulatory and antiviral activity of Edible Bird's Nest (EBN) against influenza A virus (IAV) infection

Journal of Ethnopharmacology ◽

10.1016/j.jep.2016.03.020 ◽

2016 ◽

Vol 185 ◽

pp. 327-340 ◽

Cited By ~ 15

Author(s):

Amin Haghani ◽

Parvaneh Mehrbod ◽

Nikoo Safi ◽

Nur Ain Aminuddin ◽

Azadeh Bahadoran ◽

...

Keyword(s):

Antiviral Activity ◽

Influenza A Virus ◽

Influenza A ◽

Edible Bird’S Nest

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Inhibitory Activity of Honeysuckle Extracts against Influenza A Virus In Vitro and In Vivo

Virologica Sinica ◽

10.1007/s12250-020-00302-6 ◽

2020 ◽

Author(s):

Mengwei Li ◽

Yuxu Wang ◽

Jing Jin ◽

Jie Dou ◽

Qinglong Guo ◽

...

Keyword(s):

Influenza A Virus ◽

Inhibitory Activity ◽

Influenza A

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Influenza A Virus Inhibits RSV Infection via a Two-Wave Expression of IFIT Proteins

Viruses ◽

10.3390/v12101171 ◽

2020 ◽

Vol 12 (10) ◽

pp. 1171

Author(s):

Yaron Drori ◽

Jasmine Jacob-Hirsch ◽

Rakefet Pando ◽

Aharona Glatman-Freedman ◽

Nehemya Friedman ◽

...

Keyword(s):

Influenza A Virus ◽

Influenza A ◽

Influenza Viruses ◽

Mass Spectrometry Analysis ◽

Influenza A Viruses ◽

Rsv Infection ◽

Syncytial Virus ◽

Mouse Lungs

Influenza viruses and respiratory syncytial virus (RSV) are respiratory viruses that primarily circulate worldwide during the autumn and winter seasons. Seasonal surveillance has shown 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 A virus inhibits RSV, human cervical carcinoma (HEp2) cells or mice were co-infected with influenza A and RSV. Influenza A inhibited RSV growth, both in vitro and in vivo. Mass spectrometry analysis of mouse lungs infected with influenza A identified a two-wave pattern of protein expression upregulation, which included members of the interferon-induced protein with the tetratricopeptide (IFITs) family. Interestingly, in the second wave, influenza A viruses were no longer detectable in mouse lungs. In addition, knockdown and overexpression of IFITs in HEp2 cells affected RSV multiplicity. In conclusion, influenza A infection inhibits RSV infectivity via upregulation of IFIT proteins in a two-wave modality. Understanding the immune system involvement in the interaction between influenza A and RSV viruses will contribute to the development of future treatment strategies against these viruses.

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