Antiviral Activity of the Long Chain Pentraxin PTX3 against Influenza Viruses

Abstract

Proteins of the innate immune system can act as natural inhibitors of influenza virus, limiting growth and spread of the virus in the early stages of infection before the induction of adaptive immune responses. In this study, we identify the long pentraxin PTX3 as a potent innate inhibitor of influenza viruses both in vitro and in vivo. Human and murine PTX3 bound to influenza virus and mediated a range of antiviral activities, including inhibition of hemagglutination, neutralization of virus infectivity and inhibition of viral neuraminidase. Antiviral activity was associated with binding of the viral hemagglutinin glycoprotein to sialylated ligands present on PTX3. Using a mouse model we found PTX3 to be rapidly induced following influenza infection and that PTX3−/− mice were more susceptible than wild-type mice to infection by PTX3-sensitive virus strains. Therapeutic treatment of mice with human PTX3 promoted survival and reduced viral load in the lungs following infection with PTX3-sensitive, but not PTX3-resistant, influenza viruses. Together, these studies describe a novel antiviral role for PTX3 in early host defense against influenza infections both in vitro and in vivo and describe the therapeutic potential of PTX3 in ameliorating disease during influenza infection.

The cell surface mucin MUC1 limits the severity of influenza A virus infection

“…This difference may reflect steric hindrance of receptor-binding sites on adjacent monomers of the trimeric HA molecule. This function is reminiscent of the naturally occurring g-inhibitors of IAV, such as surfactant protein A 41 and PTX3, 42 which inhibit IAV infection by blocking HA receptor-binding function. It will be interesting to compare these synthetic inhibitors with the natural inhibitors in vitro and in vivo.…”

Neutrophils Ameliorate Lung Injury and the Development of Severe Disease during Influenza Infection

“…Neutrophils themselves have been reported as both nonpermissive (6) and susceptible to influenza virus infection (71,72) and to respond to virus exposure via TLR7-and/or TLR8-mediated production of proinflammatory cytokines (71). Neutrophil granules, including azurophil/primary, secondary, and secretory granules, contain an array of molecules with potential for antiviral activity, including ␣ and ␤ defensins and pentraxins, which have been shown to exert antiviral activities against a range of viruses, including influenza (73)(74)(75).…”

HDL in Infectious Diseases and Sepsis

“…Similarly to short pentraxins, PTX3 recognizes the highly conserved pathogen-associated molecular patterns (PAMPs) expressed by microorganisms (Iwasaki and Medzhitov 2010) and binds a number of bacteria, fungi, and viruses. A specific binding has been observed to conidia of Aspergillus fumigatus (Garlanda et al 2002), Paracoccidioides brasiliensis, and zymosan (Diniz et al 2004), to selected Gram-positive and Gram-negative bacteria (Bozza et al 2006;Garlanda et al 2002;Jeannin et al 2005), and finally to some viral strains, including human and murine cytomegalovirus and influenza virus type A (IVA) (Bozza et al 2006;Reading et al 2008). Both short pentraxin and PTX3 bind apoptotic cells and facilitate their clearance (Doni et al 2012;Jaillon et al 2009).…”