H5 and H7 subtypes are associated with the highly pathogenic form of AI (HPAI), which are extremely virulent, causing up to 100% mortality in domestic poultry. This virulence and ability to cause systemic infection have been attributed to the multibasic cleavage motif in their hemagglutinin molecule, which are recognized by subtilisin-like endoproteases that are virtually present in every tissue, making them capable of replicating in multiple tissue; hence, lesions are multisystemic (i.e.,

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... us, circulatory, respiratory, integumentary, musculoskeletal, hemopoietic, gastrointestinal, reproductive systems). The myriads of lesion that accompanied outbreaks of HPAI in domestic poultry as seen in Nigeria from 2006 to 2016 are as a result of the above findings. A critical look at the Nigerian HPAI situation not only revealed the general clinic-pathologic features in domestic poultry and factors that support the persistence of the virus in the environment but also gave insight to the flow of the virus in the country. A situation whereby poultry are kept in free-range, multispecies, multiage holdings with low biosecurity supports the spread of HPAI. Also, the live bird markets (LBMs) that have been fed by this unorganized poultry structure have consistently been the nidus for HPAI detection, be it in 2008 after the virus was thought to have been eradicated or in 2015, when the virus resurfaced in Lagos. It is proposed that all factors enhancing the propensity of the virus to remain in poultry should be giving the attention required. Therefore, it is important that the strict biosecurity measures that ensure prevention of HPAI incursion into poultry premises after 2008 are revamped while improving on the organization of the poultry and product supply chain in the country.