Identification of hemagglutinin structural domain and polymorphisms which may modulate swine H1N1 interactions with human receptor

Analyses by ISM bioinformatics platform of the HA1 protein of North American swine H1N1/N2 viruses and the new A/H1N1 showed that both groups of viruses differed in conserved characteristics that reflect a distinct propensity of these viruses to undergo a specific interaction with swine or human host proteins or receptors. Swine H1N1/N2 viruses that sporadically infected humans featured both the swine and the human interaction pattern. Substitutions F71S, T128S, E302K, M314L in HA1 of swine H1N1 viruses from North America are identified as critical for the human interaction pattern of A/H1N1 and residues D94, D196 and D274 are predicted to be "hot-spots" for polymorphisms which could increase infectivity of A/H1N1 virus. At least one of these residues has already emerged in the A/H1N1 isolates from Spain, Italy and USA. The domain 286-326 was identified to be involved in virus/receptor interaction.Our results (i) contribute to better understanding of the origin of the novel A/H1N1 influenza virus, (ii) provide a tool for monitoring its molecular evolution (iii) predicts hotspots associated with enhanced infectivity in humans and (iv) identify therapeutic and diagnostic targets for prevention and treatment of A/H1N1 infection.Sporadic infections of humans by swine influenza viruses have been reported from the United States and worldwide, mostly from classical swine influenza [1-3]. During the late nineties multiple subtypes of triple reassortants influenza viruses with genes from avian, human and pig origin emerged and became predominant in North American swine [1,4]. Triple reassortant H1N1 and H1N2 subtypes occasionally infected humans but human to human transmission was rare and always very limited. However, disease severity and clinical out-come was always unpredictable [5-7]. In April 2009 a H1N1 triple reassortant swine influenza virus infected humans in North America [4] and continued to effectively transmit from human to humans (REF). The virus spread rapidly