Glycosylation as a Target for Recognition of Influenza Viruses by the Innate Immune System

Abstract

Glycosylation clearly plays an important role in the life cycle of influenza viruses and certain glycosylation sites are required for the structural integrity and stability of the HA and NA glycoproteins during biosynthesis and formation of intact virions. Furthermore, glycosylation has been shown to modulate the functions of influenza glycoproteins, in particular the recognition of host cell receptors and in shielding antigenic epitopes on the viral HA. The addition of oligosaccharide moieties to the globular head of the HA does, however, correlate with an increased sensitivity to the antiviral activities of SP-D and to recognition and destruction of virus via the MMR on murine macrophages. Consequently, the degree of glycosylation appears to be an important factor in determining sensitivity to lectin-mediated defences, and therefore in determining the ability of a particular virus strain to replicate in the respiratory tract of mice following intranasal infection. The mouse-adapted PR8 strain which lacks mannose-containing glycans from the head of its HA molecule was largely resistant to the antiviral activities of SP-D and the MMR in vitro and induced severed clinical disease following intranasal infection of mice. The finding that mannan treatment of BJx109-infected mice facilitated an early and dramatic enhancement of disease severity is also consistent with a major role for mannose-specific lectins in limiting influenza virus growth and spread in the respiratory tract.

Dendritic Cell Activation by Recombinant Hemagglutinin Proteins of H1N1 and H5N1 Influenza A Viruses

“…The N-linked glycans of influenza virus HA have been shown to regulate receptor binding and neutralization activity against influenza virus infection (38) and also to be important in influenza virus recognition by the innate immune system (26). …”

Pandemic H1N1 Influenza A Viruses Are Resistant to the Antiviral Activities of Innate Immune Proteins of the Collectin and Pentraxin Superfamilies

“…In humans, members of the collectin family that mediate antiviral activity against influenza viruses in vitro include surfactant protein (SP)-D, SP-A, and MBL. SP-D and MBL bind to mannose-rich glycans on the hemagglutinin (HA) and neuraminidase (NA) glycoproteins of different virus strains to inhibit the hemagglutinating activity of the virus (13)(14)(15), neutralize virus infectivity (14-16), aggregate virions (14,(16)(17)(18), and inhibit the enzymatic activity of the viral NA (19,20). SP-D is particularly potent in its ability to inhibit virus strains bearing high levels of glycosylation on the globular head of HA (14,15,21,22).…”

Transcriptional expression levels of chicken collectins are affected by avian influenza A virus inoculation

“…Collectins are thought to bind carbohydrate residues present on influenza hemagglutinin and neuraminidase, thereby aggregating viral particles and preventing invasion of host cells (Reading et al, 2007). In addition, a highly reduced clearance of influenza virus was observed in mice lacking either surfactant protein A or surfactant protein D, implicating the importance of these mammalian collectins in defense against influenza virus inoculations in vivo (Sano and Kuroki, 2005).…”