Understanding the landscape of cross-species transmission, epidemiology, phylogenetics, and antigenicity of HPAI strain A(H5N1) causing a recent outbreak in the USA

H5N1 virus infections have repeatedly been reported among wild birds in the USA and throughout the globe. Therefore, the recent outbreak of HPAI strain A(H5N1) in the USA is a global concern that spread among twelve states and three humans in dairy cattle farms. The virus has been reported from cow milk. In this study, we analyzed cross-species transmission, epidemiology, phylogenetics, and virus antigenicity. We depicted different phylogenetic trees using eight genome segments with 1188 genomes (n = 1188) collected from the USA, and the genome clustering at the leaf node level was shown. Here, our analysis found nine different clades. Among these nine clades, 2.3.4.4b clades have spread in the USA. The clade is currently more widespread than the others. Similarly, we have also estimated the transmission in the USA, which shows the cross-species transmission. The study shows the conservation pattern, mutation, and epitopes of two surface proteins, HA and NA. On the other hand, we depicted some significant mutations in different proteins during the outbreak. We found about 11 B-cell epitopes of HA, 15 B-cell epitopes of NA protein, and a possible epitope patch in A-chain of HA. These results suggest that the epitope might be effective for vaccine design against circulating HPAI strain A(H5N1) virus.