Lethal nephrotropism of an H10N1 avian influenza virus stands out as an atypical pathotype.

A nephrotropic H10N1 avian influenza virus (AIV) with an intravenous pathogenicity index (IVPI) of 1.9 and a haemagglutinin monobasic amino acid cleavage site motif, was genetically and phenotypically characterized. Specific pathogen free chickens of 3 or 6 weeks of age were challenged with a 10(6)EID50/0.1mL dose by either oro-nasal or intravenous route, to study the distribution, tissue tropism and virulence of the virus. Direct transmission was tested by introducing sentinel birds on day 4 post infection. Virus shedding and viremia were investigated by means of type A influenza real-time RT-PCR. Dead birds were necropsied and selected organs were collected for histology, immunohistochemistry, and to detect and re-isolate the virus. Serological analyses were carried out to evaluate seroconversion, three weeks from challenge. The oro-nasal challenge of the 6-week-old birds elicited 47% mortality as a result of viremia and massive replication of the virus in the kidneys. Unexpectedly, among birds of 3 weeks of age the same challenge caused 5% mortality and few clinical signs. Surprisingly the intravenous administration of the virus in the 3-week-old birds recorded an IVPI of 2.4. A full genome characterization of the virus could not identify any molecular determinant underlying the observed phenotype. Our findings describe the complex pathobiology of an AIV of the H10 subtype that stands out for its peculiar pathogenicity and tissue tropism in chickens.