Prediction of Biological Functions on Glycosylation Site Migrations in Human Influenza H1N1 Viruses

Shisheng Sun,Qinzhe Wang,Fei Zhao,Wentian Chen,Zheng Li,Jean-Pierre Vartanian

doi:10.1371/journal.pone.0032119

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.

Highlights

Influenza virus can cause occasional pandemics and seasonal epidemics in humans [1]
Glycosite 144 appeared on the top of the HA head in human influenza H1N1 viruses in 1940 and was replaced by glycosite 172 in 1947 (Figure S1) [25]
Homology modeling and in silico protein glycosylation of representative HA and NA proteins as well as amino acid variability analysis at antigenic sites were employed for predicting biological functions of glycosite migrations in the host adaptation of human seasonal influenza H1N1 viruses

Summary

Introduction

Influenza virus can cause occasional pandemics and seasonal epidemics in humans [1]. While on the other hand, the pandemic virus undergoes gradual changes in its antigenic structure (called antigenic drift) so as to escape the immune pressure imposed by the host. Such pressure and drift lead to the transformation of the pandemic virus to a seasonal one as well as the subsequent evolution of the seasonal influenza virus [1,2,3,4]. Protein glycosylation is believed to be involved in the evolution of influenza viruses [5,6]. The HA and NA glycosylation of an influenza strain can affect its host specificity, virulence and infectivity either directly, by changing the biologic properties of HA and NA [8], or indirectly, by attenuating receptor binding [9,10,11,12,13], masking antigenic regions of the protein [14,15,16], impeding the activation of the protein precursor HA0 via its cleavage into the disulfide-linked subunits

Methods

Results

Conclusion