Virtual High Throughput Screening (vHTS) derivation of a cross-immunity model for the Influenza-A Virus Infections

Funding: OPUS, NCN
Project period: 2014 - 2017
Project leader: Dariusz PlewczyƄski

Centre of New Technologies, University of Warsaw

Research project objectives:

The project proposes a novel in silico framework for the population level molecular and genetic analyses of the hemagglutinin (HA) gene coding the main antigen of influenza IV strain. The HA gene shows the high degree of polymorphism, correlated with elevated mutation rate of viruses, which allow influenza viruses to escape from hosts’ immunological control. We would like to identify the extent of HA genetic diversification, which is imposed by the shape and the active site surface of which have to be optimally adapted to its function, namely the recognition of sialic acid glycan derivates, initiating infection of the host cell. Up to now, most of the research efford was devoted to epitopes diversification

 Expected impact of the research project on the development of science, civilization and society:

To give the effort proposed here a more broad perspective – our very long-term aim is to build a descriptive model of large scale phylogenetic propagation of hemagglutinin mutations in heterogeneous populations of hosts: human and zoonotic. This will be important as a possible next step development basis for individual to individual host–pathogen interaction simulations, implemented as the country-wide epidemiological Monte Carlo simulation models for Poland – already devised, implemented and validated by us earlier.

Influenza A is a serious disease causing recurrent outbreaks with tremendous impact on global health and economy. In April 2009 a novel H1N1 swine-origin influenza A (usually designated now as A/H1N1/v) was reported in Mexico and United States. Within several months from its emergence, the virus spread to over 70 other countries. This urged the WHO to raise its pandemic alert level to the highest phase 6 on June 11, 2009. The 2009 pandemic influenza A turned out to be relatively mild, when compared to other strains responsible for the previous pandemics. Most individuals infected with the 2009 pandemic H1N1 strain usually developed uncomplicated illness with full recovery within a week, although some age groups (mostly young people, and elderly with specific chronic illnesses) were subjected to severe health complications. However, this may be a transient situation because influenza viruses are constantly undergoing changes, and the infection with future strains may increase in severity. We should bear in mind that the 1918 Spanish flu pandemic virus was relatively mild in its first wave, but acquired higher virulence, when it returned in the next season.