Prediction of biological functions on glycosylation site migrations in human influenza H1N1 viruses

Abstract

Protein glycosylation alteration is typically employed by various viruses for escaping immune pressures from their hosts. Our previous work had shown that not only the increase of glycosylation sites (glycosites) numbers, but also glycosite migration might be involved in the evolution of human seasonal influenza H1N1 viruses. More importantly, glycosite migration was likely a more effectively alteration way for the host adaption of human influenza H1N1 viruses. In this study, we provided more bioinformatics and statistic evidences for further predicting the significant biological functions of glycosite migration in the host adaptation of human influenza H1N1 viruses, by employing homology modeling and in silico protein glycosylation of representative HA and NA proteins as well as amino acid variability analysis at antigenic sites of HA and NA. The results showed that glycosite migrations in human influenza viruses have at least five possible functions: to more effectively mask the antigenic sites, to more effectively protect the enzymatic cleavage sites of neuraminidase (NA), to stabilize the polymeric structures, to regulate the receptor binding and catalytic activities and to balance the binding activity of hemagglutinin (HA) with the release activity of NA. The information here can provide some constructive suggestions for the function research related to protein glycosylation of influenza viruses, although these predictions still need to be supported by experimental data.

Figure 1. Structural overviews of the glycans attached to glycosites 179 (A) and 177(B) and their shielding regions on HA of human seasonal influenza H1N1 viruses.

The glycosites are numbered in white.

Figure 2. Amino acid variability at antigenic sites of HA (A) and NA (B) in human seasonal influenza H1N1 viruses.

The variability was the total number of amino acids present at each antigenic region in the group of isolates with specific glycosite pattern. The numbers of corresponding strains in each group used for the analysis are given in the brackets.

Figure 3. Structural overviews of the glycans attached to glycosites 144 (A), 172 (B) and 142 (C) and their shielding regions on HA of human seasonal influenza H1N1 viruses.

The glycosites are numbered in white.

Figure 4. Structural overviews of the glycans attached to glycosites 104 (A), 286 (B) and 71 (C) and their shielding regions on HA of human seasonal influenza H1N1 viruses.

The glycosites are numbered in white.

Figure 5. Structural overviews of the glycosylated tetramer from A/Singapore/6/1986 (A) and the shielding regions of the glycans attached to glycosites in region C, including glycosites 146 (B), 365 (C) and 434 (D).

The glycosites are numbered in white.