Playing Hide and Seek: How Glycosylation of the Influenza Virus Hemagglutinin Can Modulate the Immune Response to Infection

Abstract

Seasonal influenza A viruses (IAV) originate from pandemic IAV and have undergone changes in antigenic structure, including addition of glycans to the hemagglutinin (HA) glycoprotein. The viral HA is the major target recognized by neutralizing antibodies and glycans have been proposed to shield antigenic sites on HA, thereby promoting virus survival in the face of widespread vaccination and/or infection. However, addition of glycans can also interfere with the receptor binding properties of HA and this must be compensated for by additional mutations, creating a fitness barrier to accumulation of glycosylation sites. In addition, glycans on HA are also recognized by phylogenetically ancient lectins of the innate immune system and the benefit provided by evasion of humoral immunity is balanced by attenuation of infection. Therefore, a fine balance must exist regarding the optimal pattern of HA glycosylation to offset competing pressures associated with recognition by innate defenses, evasion of humoral immunity and maintenance of virus fitness. In this review, we examine HA glycosylation patterns of IAV associated with pandemic and seasonal influenza and discuss recent advancements in our understanding of interactions between IAV glycans and components of innate and adaptive immunity.

A Bioinformatics Study of Complete Amino Acid Sequences’ Changes of Hemagglutinin Antigen of H1N1 Influenza Viruses in GenBank From Year 2006 to 2013 in Iran

“…It is of considerable importance to detect new antigenic changes occurring in HA protein when updating vaccine compositions. The results of our study are consistent with the results of others in terms of changes in number and location of glycosylation sites (20,21), mutations/conservation in important positions such as Q240R (22), V169T, and D239G (24,25), changes/conservation in active/binding sites (23,24), and conservation in important domains such as fusion peptide (24,25). Evaluation of changes in predicted ligandbinding sites, type and number of ligands was done in our study, which indicated a significant change in ligand binding site of 2009 isolates.…”

“…The presence of glycosylation sites, which are commonly conserved, mask the protein surface from recognition by an antibody. Addition of glycans to the HA is an important mechanism contributing to antigenic drift and therefore sustained circulation of influenza A virus in the human population (20,21). The (Table 3), in which some changes (creation/ deletion of glycosyla- Position 240, which is located in receptor binding site, is one of the important positions in HA (22).…”

Predominance of influenza A(H1N1)pdm09 virus genetic subclade 6B.1 and influenza B/Victoria lineage viruses at the start of the 2015/16 influenza season in Europe

“…However, the antigenic reports rely on national influenza centres' antigenic analysis that the viruses reported as like to vaccine virus were not more than fourfold different in HI titres from the vaccine or reference viruses. Further enhancement of the antigenicity and virulence of influenza virus has been attributed to shielding of the major antigenic epitopes by alteration of N-linked glycosylation sites [18]. D127E substitution seen in 6B.2 has been associated with antigenic change of other influenza viruses through modelling [17].…”

A surprising sweetener from enteropathogenicEscherichia coli

“…4 Surface glycans serve as ligands for glycan-binding proteins in cellular trafficking, adhesion and signaling events 5,6 and also mediate interactions between the vertebrate host and microbial pathogens. [7][8][9] Other processes influenced by glycan structures include innate immune signaling, autoimmune reactions and tumor metastases. 2,8 Glycan structure is determined by the concerted action of numerous genes that code for glycosyltransferases, glycosidases, and other enzymes that synthesize and remodel glycan chains, as well as accessory enzymes involved in the synthesis and transport of nucleotide sugars.…”