Host-pathogen interactions during coronavirus infection of primary alveolar epithelial cells

Abstract

Viruses that infect the lung are a significant cause of morbidity and mortality in animals and humans worldwide. Coronaviruses are being associated increasingly with severe diseases in the lower respiratory tract. Alveolar epithelial cells are an important target for coronavirus infection in the lung, and infected cells can initiate innate immune responses to viral infection. In this overview, we describe in vitro models of highly differentiated alveolar epithelial cells that are currently being used to study the innate immune response to coronavirus infection. We have shown that rat coronavirus infection of rat alveolar type I epithelial cells in vitro induces expression of CXC chemokines, which may recruit and activate neutrophils. Although neutrophils are recruited early in infection in several coronavirus models including rat coronavirus. However, their role in viral clearance and/or immune-mediated tissue damage is not understood. Primary cultures of differentiated alveolar epithelial cells will be useful for identifying the interactions between coronaviruses and alveolar epithelial cells that influence the innate immune responses to infection in the lung. Understanding the molecular details of these interactions will be critical for the design of effective strategies to prevent and treat coronavirus infections in the lung.

Association of seropositivity for influenza and coronaviruses with history of mood disorders and suicide attempts

“…The immune response to influenza and coronaviruses involves cell-mediated immunity, antibody-mediated immunity, local production of antibodies, interferon and other host defenses. In addition, systemic symptoms are felt to be related to the production of cytokines including tumor necrosis factorα, interleukin 6 and 8, and interferon-α (Dolin, 2008;Miura and Holmes, 2009).…”

Human Coronavirus HKU1 Infection of Primary Human Type II Alveolar Epithelial Cells: Cytopathic Effects and Innate Immune Response

“…This supports our hypothesis that primary human alveolar cells can be a suitable culture system for isolation and propagation of novel human respiratory viruses that cause lower respiratory tract disease and which display a stringent degree of cell, tissue, and host specificity. Utilization of this culture system is appealing because it most closely represents the in vivo physiological conditions of the lung [2,21]. The type II culture system allows identification of which terminal human respiratory epithelial cells are susceptible to infection and might provide insight into the spread of infections from the conducting airways required for the development of pneumonia and the acute respiratory distress syndrome (ARDS).…”

“…Because they are the natural target cells for respiratory virus infection, primary human respiratory epithelial cell cultures provide the ideal in vitro systems for investigation of cell factors required for growth of respiratory human viruses, for analysis of their interactions with viruses and their innate immune responses to infection, and for isolation and propagation of novel respiratory pathogens. The alveolar epithelium consists of both alveolar type I cells (ATI), which make up 95% of the surface area of the lung, are terminally differentiated, non-dividing, and function in gas exchange and fluid homeostasis; and alveolar type II cells (ATII), which produce surfactant proteins and lipids, divide and differentiate to replace damaged ATI cells, participate in fluid homeostasis, and contribute to the innate defenses of the lung [1,2,3,4]. Our laboratory has developed a system to isolate and culture primary ATII cells from human lungs and under specialized culture conditions transdifferentiate the ATII cells into an ATI-like phenotype [5].…”

Cationic Host Defence Peptides: Potential as Antiviral Therapeutics

“…Antiviral activity of retrocyclins has also been reported against SARS virus, a coronavirus which infects the alveolar epithelial cells and induces rapid severe lung pathology [127,128]. In a mouse model of SARS infection, RTD-1 treatment increased survival from 25 to 100 %.…”