Infection with human coronavirus NL63 enhances streptococcal adherence to epithelial cells

Abstract

Understanding the mechanisms of augmented bacterial pathogenicity in post-viral infections is the first step in the development of an effective therapy. This study assessed the effect of human coronavirus NL63 (HCoV-NL63) on the adherence of bacterial pathogens associated with respiratory tract illnesses. It was shown that HCoV-NL63 infection resulted in an increased adherence of Streptococcus pneumoniae to virus-infected cell lines and fully differentiated primary human airway epithelium cultures. The enhanced binding of bacteria correlated with an increased expression level of the platelet-activating factor receptor (PAF-R), but detailed evaluation of the bacterium-PAF-R interaction revealed a limited relevance of this process. INTRODUCTIONThe concept of excessive morbidity and mortality of bacterial infection occurring during or shortly after viral infection was first formulated for influenza virus in the early 19th century. Analysis of influenza pandemics showed that the incidence of bacterial pneumonia was increased and contributed substantially to mortality rates (Abrahams et al., 1919;Muir & Wilson, 1919;Stone & Swift, 1919;Wilson & Steer, 1919). Comparison of bacteriological and virological data from children hospitalized for respiratory disease shows a high degree of occurrence of viral and bacterial infections positively correlating with the severity of illness (Duttweiler et al., 2004;Kneyber et al., 2005;Randolph et al., 2004;Thorburn et al., 2006). Although the role of a preceding viral infection in development and severity of bacterial respiratory diseases is a clinically welldocumented phenomenon, the exact mechanism has not been elucidated fully.Initially, it was proposed that respiratory viruses facilitate bacterial colonization through physical damage of the respiratory tract epithelium, with exposed basement membrane components being responsible for increased bacterial adherence (Louria et al., 1959;Muir & Wilson, 1919;Wilson & Steer, 1919;Wolbach, 1919). Such a mechanism undoubtedly occurs for highly pathogenic viral species, but it does not explain the occurrence of increased severity of bacterial infection during and shortly after relatively mild viral infections. Analysis of published data suggests that interplay between viruses and bacteria is a complex process, where the final outcome depends heavily on multiple factors, including modulation of innate immune responses resulting in delayed clearance of bacteria, hypersensitization of infected cells leading to enhanced immune-mediated lung damage and modulation of bacterial adherence (Okamoto et al., 2004). The increase in bacterial adherence occurs due to exposure of novel binding sites for bacteria on the epithelial surface, either by expression of highly glycosylated viral proteins (McCullers & Bartmess, 2003;Peltola & McCullers, 2004) or by the alteration of a bacterial receptor expression pattern (McCullers & Rehg, 2002;Patel et al., 1995;Terajima et al., 1997).Bacterial pathogens predominantly involved in secondary infection of the r...

Bovine respiratory syncytial virus infection enhances Pasteurella multocida adherence on respiratory epithelial cells

“…Previously, we confirmed that HRSV infection upregulates expression of platelet-activating factor receptor (PAF-R), a receptor for S. pneumonia, on A549 (Yokota et al, 2010). Similar phenomena are observed during infection with rhinovirus and coronavirus, which upregulate expression of fibronectin, carcinoembryonic antigen-related cell adhesion molecule, and PAF-R on respiratory epithelial cells (Ishizuka et al, 2003;Golda et al, 2011). However, little is known about how PM attaches to virus-infected respiratory cells.…”

Novel polymeric inhibitors of HCoV-NL63

“…To rule out such a possibility, a quantitative RT-PCR -based assay was employed to assess the HCoV-NL63 yield in the cell culture supernatant. The assay was performed as previously described (Golda et al, 2011) and the number of RNA copies per milliliter of cell culture supernatant was assessed. Conducted analysis clearly shows that in the presence of the studied polymers there is a significant decrease in the number of viral copies produced during infection (Fig.…”

Viral–bacterial interactions in the respiratory tract

“…Increased attachment of bacteria to virus-infected cells and tissue has been observed for numerous combinations of respiratory pathogens, some of which will be discussed in more detail below (Avadhanula et al, 2006;Golda et al, 2011;Ha kansson et al, 1994;Hament et al, 2004;Jiang et al, 1999;Raza et al, 1993;Sanford & Ramsay, 1987;Wang et al, 2009). Generally, bacterial attachment can be enhanced by (1) increased expression of host receptors after viral infection or (2) by viral structures serving as coupling agents for bacteria to host tissues.…”