In silico genetic variation pathogenicity analysis of hemagglutinin, matrix 1, and non structural 1 protein of human H5N1 Indonesian strain

Avian influenza (H5N1) is a disease caused by type A influenza viruses. Although in general influenza type A is not lethal to humans, several cases did. In silico mutation analysis could be utilized using multiple alignment methods, AminoTrack server, and phylogenetic tree. Mutations were observed for the cleavage site of haemagglutin (HA) protein, while for the Non-Structural 1 (NS1) and Matrix1 (M1) mutations was observed on their entire region. It was followed by prediction of the pro-P (furin) HA specific cleavage, secondary structure, mutation (exposed/buried) prediction, epitope prediction, and 3D structures prediction. Based on the analysis of mutations in the HA cleavage site, the conserved pattern for Indonesia and Hong Kong H5N1 is RXK/RR, while the sequence of subtype H1N1, H1N2, and H3N2 did not have it. Furin prediction showed this pattern causes the HA of H5N1 could be cleaved. Specific mutations in the NS1 control sequences: (A/Indonesia/5/2005 (H5N1), A/Indonesia/CDC1032/2007(H5N1), A/HongKong/156/97(H5N1), A/BrevigMission/1/18(H1N1), A/Mexico/InDRE4487/2009(H1N1)) with the subtype H1N1, H1N2, and H3N2 were found in position 53. Identical specific control mutation on the M1 for the three subtypes was not found. 248 positions have changes in the H1N1 and H3N2. Epitope prediction explains that control sequences NS1 and M1 of H1N1, H1N2, and H3N2 subtypes have similar IC50 values below 50 nM. Specific mutations do not occur in epitope recognition. Occurred region-specific mutations for NS1 and M1 did not affect the secondary and tertiary structure of proteins significantly compared with the controls sequences.