# title
Behl, Michelle A (2016-08). Highly Pathogenic Avian Influenza H5N2 in Naturally Infected Turkey Breeder Hens: Virus Distribution, Histopathology, and Host Immune Gene Expression. Doctoral Dissertation.

# abstract
The outbreak of the highly pathogenic avian influenza virus (HPAI) in 2014- 2015 was by far the largest animal disease outbreak in United States history. The turkey industry was the most affected as nearly 70% of the confirmed cases were in turkeys. This project examined viral distribution, semi-quantitative viral load, histological viral lesions, and gene expression of several immune components in 8 tissues of naturally infected turkey breeder hens during the outbreak. Tissues from clinically and sub-clinically affected turkeys, as well as negative controls were obtained: brain, heart, GI, liver, lung, reproductive tract, spleen, and trachea. Changes in the gene expression of IL-1β, IL-6, IL-10, CCL-5, CXCLi-2, Mx, OASL, IFN-γ, IFIH1, FasL and TRAIL were described.   The matrix gene was detected in all 8 of the tissues collected from the clinical and sub-clinical groups. The clinically affected turkeys had significantly higher levels of matrix gene detected in the brain, GI, spleen, and trachea. Histological viral lesions were in general very mild and insignificant. The majority of the histological changes were confined to the trachea and liver and primarily consisted of the infiltration of small numbers of heterophils, lymphocytes, and macrophages. This particular virus was able to evade the host’s immune response using several tactics. It was able to avoid initial detection by suppressing IFIH1 expression, the pro-inflammatory cytokines IL-1β and IL-6, and the antiviral component IFN-γ in the trachea. Undetected, the virus quickly disseminated throughout the body and replicated rapidly. The widespread downregulation of IFN-γ and upregulation of CCL-5 and OASL likely contributed to the pathogenesis.   Virus was detected in all of the tissues collected on the positive premise, regardless of clinical status thus illustrating its extreme infectivity. Generally, histological lesions were minimal and cytokine responses were not excessive. Death does not appear to be the result of organ damage/necrosis or even cytokine storm, but purely from immune evasion and excessive viral load in the tissues. Consequently the high viral loads in the tissues resulted in organ failure.

# websites[].label
Highly Pathogenic Avian Influenza H5N2 in Naturally Infected Turkey Breeder Hens: Virus Distribution, Histopathology, and Host Immune Gene Expression