Influenza virus and endothelial cells: a species specific relationship

Abstract

Influenza A virus (IAV) infection is an important cause of respiratory disease in humans. The original reservoirs of IAV are wild waterfowl and shorebirds, where virus infection causes limited, if any, disease. Both in humans and in wild waterbirds, epithelial cells are the main target of infection. However, influenza virus can spread from wild bird species to terrestrial poultry. Here, the virus can evolve into highly pathogenic avian influenza (HPAI). Part of this evolution involves increased viral tropism for endothelial cells. HPAI virus infections not only cause severe disease in chickens and other terrestrial poultry species but can also spread to humans and back to wild bird populations. Here, we review the role of the endothelium in the pathogenesis of influenza virus infection in wild birds, terrestrial poultry and humans with a particular focus on HPAI viruses. We demonstrate that whilst the endothelium is an important target of virus infection in terrestrial poultry and some wild bird species, in humans the endothelium is more important in controlling the local inflammatory milieu. Thus, the endothelium plays an important, but species-specific, role in the pathogenesis of influenza virus infection.

Prevalence of the C-terminal truncations of NS1 in avian influenza A viruses and effect on virulence and replication of a highly pathogenic H7N1 virus in chickens

“…27 Decreased replication in the brain in birds infected with Hp-NS230 or Hp-NSLp may be due to decreased tropism to endothelial cells; which is an important feature of HPAIV in domestic poultry. 28 These results indicated that NS1 can (1) modulate tropism to different tissues limiting systemic spread of the virus and (2) truncation is involved in this restriction but also other mutations in the NS1 play an additional role. Previously, it has been shown that the NS1 gene facilitates spread of HPAIV H5N1 from the lung to the brain of experimentally infected mice.…”

Respiratory Antiviral Immunity and Immunobiotics: Beneficial Effects on Inflammation-Coagulation Interaction during Influenza Virus Infection

“…A key role has been attributed to ECs in the temporal and special regulation of coagulation activation. Resting ECs avoid the inappropriate plug formation by controlling platelet adhesion and activation and generating several anticoagulant factors providing a non-thrombogenic barrier (55, 56). Once activated or injured, ECs expose collagen to blood, increase platelet binding and aggregation, reduce the expression physiological anticoagulant factors, increase the expression of TF and von willebrand factor, and suppress the fibrinolytic activity (57, 58).…”

“…Influenza is able to cause pulmonary hemorrhage and edema related to coagulopathy or induce uncontrolled thrombosis through an over-activated coagulation (Figure 3) (55, 58). Animal models have helped to explain the mechanisms by which IFV infection activates coagulation and key role has been attributed to TF.…”

Original Antigenic Sin Response to RNA Viruses and Antiviral Immunity

“…Differences between dengue and influenza viruses in this regard, might result in different OAS effects. Influenza viruses have not been shown to productively infect FcR-bearing immune cells or endothelial cells in humans (61). However, inflammatory responses originating from virus-antibody-complement-complement receptor complexes on pulmonary endothelial cells and other FcR- and complement receptor-bearing myeloid lineage cells (5762) cannot be ruled out.…”