We previously reported that nucleoproteins (NPs) of human influenza viruses are cleaved in infected cells and, as a result, two forms of NP, uncleaved (mol. wt. 56000) and cleaved (mol. wt. 53000) were accumulated late in infection. Here, we report that NPs of animal influenza viruses of non-human origin (isolated from pigs, equids, seals, whales, birds) exhibited proteolytic resistance in infected cells and did not undergo a change in mol. wt. in the course of infection. The resistance of the animal virus NPs to proteolytic cleavage was shown to be a virus-specific property and not the consequence of a low level of proteolysis in infected cells. Influenza A/H3N2 viruses isolated from swine in Hong Kong in 1976 were found to have a cleavable NP like that of ‘human’ viruses, supporting the hypothesis concerning the ‘human’ origin of these strains. The NP of human influenza virus (A/Aichi/2/68) adapted to an animal host (mouse) retained susceptibility to limited intracellular proteolysis. Thus, NP resistance to cleavage seems to be a stable viral characteristic enabling the NP56→NP53 modification to be used as an indication of the origin of influenza viruses.


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