Effects of Influenza A Nucleoprotein on Polymorphonuclear Neutrophil Function

Abstract

Infection with influenza virus is commonly associated with polymorphonuclear neutrophil (PMNL) dysfunction and consequent secondary bacterial pneumonia. A recently isolated human-derived protein that inhibits PMNL chemotaxis and oxidant production shows a striking homology to the influenza A nucleoprotein. In the present study, the effects of purified influenza A nucleoprotein on PMNL chemotaxis, oxidant production, degranulation, and calcium homeostasis were studied. Results of the study demonstrate that purified nucleoprotein inhibits PMNL chemotaxis as well as superoxide production. In addition, purified nucleoprotein induces a rise in PMNL cytosolic calcium concentration in a manner similar to that demonstrated for crude influenza A lysates. In contrast, no difference in FMLP-stimulated PMNL elastase or beta glucuronidase release was noted after exposure to nucleoprotein. These studies suggest that the influenza A nucleoprotein may account for some of the neutrophil defect associated with cellular infection by this virus.

Neutrophils: Neglected Players in Viral Diseases

“…Moreover, EBV has been reported to induce neutrophil apoptosis (Larochelle et al, 1998). Complementing these observations, the nucleoprotein (Cooper et al, 1996) and neuraminidase (Debets-Ossenkopp et al, 1982), proteins…”

“…Such mechanisms have been described for influenza virus, cytomegalovirus, and EBV infections where neutrophils were altered in their capacity to produce ROS (Abramson et al, 1982b(Abramson et al, , 1984Hartshorn et al, 1995;Cooper et al, 1996). In addition, they have been shown to impair the migratory (Ruutu et al, 1977;Larson et al, 1980;DebetsOssenkopp et al, 1982;Abramson et al, 1984;Cooper et al, 1996) and adhesive properties of neutrophils (Abramson et al, 1984), as well as in the release of effector proteins by degranulation (Abramson et al, 1984;Pang et al, 2000). Moreover, EBV has been reported to induce neutrophil apoptosis (Larochelle et al, 1998).…”

Technical Report: Reduction of the Influenza Burden in Children

“…11 The mechanisms by which the influenza virus is thought to contribute to the development of AOM include alteration of eustachian tube function, direct invasion of the middle ear epithelium, alteration of leukocyte function, enhancement of adherence of bacteria to respiratory tract epithelial cells, and decreased mucociliary clearance. [13][14][15][16][17][18] There is evidence that concurrent viral and bacterial middle ear infection significantly worsens the course of AOM. 19 Influenza and its complications lead to a 10% to 30% increase in the number of antimicrobial courses prescribed to children during influenza season.…”

Critical insights into the pathogenesis of clinical isolates of pandemic influenza A(H1N1) 2009 virus in mouse and ferret models.

“…Increased inflammation (due to viral determinants or chronic inflammatory disease in the host) may alter critical timing of the recruitment of immune cells, which may not be able to respond appropriately (e.g., recruited immature neutrophils do not have type I IFN receptors (530)). Moreover, IAV strains which alter specific signals, such as suppression of type I IFN production from infected cells (69,199) or disabling neutrophil responses (421,422,431,440), increase disease severity in ferrets and mice, respectively. In these scenarios, the absence of a typical "viral" lung microenvironment restricts valuable information to needed to elicit an appropriate response.…”

“…Oxidative burst is thought to have direct microbial effects, however the direct effect on IAV has not been published (436). IAV infection benefits from the presence of ROS in the environment (437,438), yet IAV also suppresses NADPH oxidase activity within infected phagocytes (439,440 …”