Host gene expression profiles in ferrets infected with genetically distinct henipavirus strains

Abstract

Henipavirus infection causes severe respiratory and neurological disease in humans that can be fatal. To characterize the pathogenic mechanisms of henipavirus infection in vivo, we performed experimental infections in ferrets followed by genome-wide gene expression analysis of lung and brain tissues. The Hendra, Nipah-Bangladesh, and Nipah-Malaysia strains caused severe respiratory and neurological disease with animals succumbing around 7 days post infection. Despite the presence of abundant viral shedding, animal-to-animal transmission did not occur. The host gene expression profiles of the lung tissue showed early activation of interferon responses and subsequent expression of inflammation-related genes that coincided with the clinical deterioration. Additionally, the lung tissue showed unchanged levels of lymphocyte markers and progressive downregulation of cell cycle genes and extracellular matrix components. Infection in the brain resulted in a limited breadth of the host responses, which is in accordance with the immunoprivileged status of this organ. Finally, we propose a model of the pathogenic mechanisms of henipavirus infection that integrates multiple components of the host responses.

Acute experimental infection of bats and ferrets with Hendra virus: Insights into the early host response of the reservoir host and susceptible model species

“…In contrast to bats, the domestic ferret (Mustela putorius furo) reliably develops fulminating disease following exposure to either HeV or NiV, with principal involvement of the vascular system and involvement of multiple organ systems including the lung, lymphoid tissues and central nervous system [14,15,16]. Although the lack of ferret specific phenotyping reagents PLOS PATHOGENS L-FW) and project grants from the National Health and Medical Research Council (NHMRC) of Australia (APP1042602 to AWP, L-FW and MLB and APP1084283 to AWP).…”

Improving immunological insights into the ferret model of human viral infectious disease

“…Emerging viruses belonging to the Paramyxoviridae family (Henipaviruses) can cause severe respiratory illness and/or encephalitis in humans. Ferrets infected with henipaviruses exhibit similar symptoms as humans including respiratory signs such as cough and nasal discharge, neural signs such as depression, and high mortality rates with most experimentally infected ferrets succumbing within 1 week . While the virus is detected in pharyngeal and rectal secretions, it is currently unclear if ferrets could serve as a transmission model for the disease .…”

“…Ferrets infected with henipaviruses exhibit similar symptoms as humans including respiratory signs such as cough and nasal discharge, neural signs such as depression, and high mortality rates with most experimentally infected ferrets succumbing within 1 week . While the virus is detected in pharyngeal and rectal secretions, it is currently unclear if ferrets could serve as a transmission model for the disease . Ferrets infected intranasally with henipaviruses similarly display clinical illness .…”

“…While the virus is detected in pharyngeal and rectal secretions, it is currently unclear if ferrets could serve as a transmission model for the disease . Ferrets infected intranasally with henipaviruses similarly display clinical illness . Assessment of immune gene expression by Leon et al in both lungs and brain tissues of the infected ferrets revealed upregulation of macrophage markers such as CD40 and CD80 in both lung and brain tissues, whereas lymphocytic markers were unchanged in the lungs.…”

“…However, for many viruses, alternative animal models better recapitulate human physiology and disease. Ferrets ( Mustela putorius furo ) have been employed to study the pathogenesis of a variety of human pathogens, including human and avian influenzas, coronaviruses including severe acute respiratory syndrome (SARS‐CoV), human respiratory syncytial virus (HRSV), human metapneumovirus (HMPV), Ebola virus and henipavirus (Nipah virus and Hendra virus) . While ferrets can be productively infected with many of these viruses, a lack of some tools to interrogate ferret immunological responses to infection limits insights that might impact the development of vaccines and/or therapeutics.…”