Abstract

The main findings of the post-mortem examination of poultry infected with highly pathogenic avian influenza viruses (HPAIV) include necrotizing inflammation and viral antigen in multiple organs. The lesion profile displays marked variability, depending on viral subtype, strain, and host species. Therefore, in this study, a semiquantitative scoring system was developed to compare histopathological findings across a wide range of study conditions. Briefly, the severity of necrotizing lesions in brain, heart, lung, liver, kidney, pancreas, and/or lymphocytic depletion in the spleen is scored on an ordinal four-step scale (0 = unchanged, 1 = mild, 2 = moderate, 3 = severe), and the distribution of the viral antigen in parenchymal and endothelial cells is evaluated on a four-step scale (0 = none, 1 = focal, 2 = multifocal, 3 = diffuse). These scores are used for a meta-analysis of experimental infections with H7N7 and H5N8 (clade 2.3.4.4b) HPAIV in chickens, turkeys, and ducks. The meta-analysis highlights the rather unique endotheliotropism of these HPAIV in chickens and a more severe necrotizing encephalitis in H7N7-HPAIV-infected turkeys. In conclusion, the proposed scoring system can be used to condensate HPAIV-typical pathohistological findings into semiquantitative data, thus enabling systematic phenotyping of virus strains and their tissue tropism.

Highlights

  • Except for two bat-derived influenza viruses (H17N10 and H18N11), all subtypes were initially isolated from birds and are classified as avian influenza viruses (AIV) [3]

  • As the first aim of this study, we propose an elaborated scoring system with a detailed explanation of scoring criteria, which was developed by critical reassessment of data and tissues from multiple infection experiments with subtype H4, H5, H7, and H9 viruses in chickens, ducks, turkeys, geese, and mammals (Table S1)

  • The first aim aimofofthis this study to develop an applicable, universal that allows standardized histological evaluationevaluation of pathologic changes caused by different system thataallows a standardized histological of pathologic changes caused avian influenza viruses

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Summary

Introduction

Influenza A virus (IAV), a genus within the Orthomyxoviridae family, is further classified based on the antigenicity of the surface proteins hemagglutinin (HA) and neuraminidase (NA) into different HxNy subtypes [1]. 18 HA (H1–H18) and 11 NA (N1–N11) subtypes are differentiated [2]. Except for two bat-derived influenza viruses (H17N10 and H18N11), all subtypes were initially isolated from birds and are classified as avian influenza viruses (AIV) [3]. AIV shows a high variability resulting from molecular changes mainly by two mechanisms: The accumulation of point mutations (antigenic drift, especially if HA is affected [4]) and reassortment of viral gene segments during co-infection with different AIV (antigenic shift, if HA and/or NA are affected) [3,5]. Even identical AIV subtypes exhibit highly variable pathogenicity and virulence even in closely related avian species [6,7]

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