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

Abstract

Influenza Other Respi Viruses. 2019;13:535-546. | 535 wileyonlinelibrary.com/journal/irv 1 | INTRODUC TI ON Animal models have proved critical in developing concepts of immunity to infection. Non-human primates (NHP) are a highly humanrelevant disease model for infectious agents due to high genetic conservation between humans and NHP. 1-3 However, significant cost and ethical issues often necessitate the use of smaller animal models for both basic and translational research. Mice (Mus musculus) are a favoured small animal model due to widespread availability, incisive transgenic models, comprehensive genomic information 4 and readily available reagents. 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), 5-14 human respiratory syncytial virus (HRSV), 15-20 human metapneumovirus (HMPV), 21 Ebola virus 22-28 and henipavirus (Nipah virus and Hendra virus). 29-34 While ferretscan 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. Here, we review recent insights gained from ferret models of human respiratory diseases, with a major focus on influenza, and highlight several knowledge gaps whose closure will greatly enhance the informational gain from ferret models to advance development of human vaccines and therapeutics. AbstractFerrets are a well-established model for studying both the pathogenesis and transmission of human respiratory viruses and evaluation of antiviral vaccines. Advanced immunological studies would add substantial value to the ferret models of disease but are hindered by the low number of ferret-reactive reagents available for flow cytometry and immunohistochemistry. Nevertheless, progress has been made to understand immune responses in the ferret model with a limited set of ferret-specific reagents and assays. This review examines current immunological insights gained from the ferret model across relevant human respiratory diseases, with a focus on influenza viruses. We highlight key knowledge gaps that need to be bridged to advance the utility of ferrets for immunological studies. K E Y W O R D S ferret, immunology, influenza How to cite this article: Wong J, Layton D, Wheatley AK, Kent SJ. Improving immunological insights into the ferret model of human viral infectious disease. Influenza Other Respi Viruses. 2019;13:535-546. https ://doi.

Rift Valley Fever Virus Infection Causes Acute Encephalitis in the Ferret

“…The ferret model fills this gap in that it is a nonrodent animal species that is readily available and less resource-intensive than NHPs. Additionally, with wide use of ferrets for influenza studies, there is a wealth of knowledge already in place, and new immunologic reagents are being actively developed (34). The ferret model recapitulates at least two important manifestations of RVFV disease that are seen in humans: mild self-limited febrile illness and later-onset severe encephalitis.…”

“…Ferrets are less expensive than NHPs and do not require the same large-animal facilities as NHPs but have been shown to similarly reproduce aspects of viral disease progression (31). Additionally, since ferrets are excellent models of influenza, many new virologic and immunologic reagents are actively being developed to make this a more useful resource for studying infectious diseases (34). RVFV was first shown to cause pathology in ferrets in 1935 (35).…”

Effects of gp120 Inner Domain (ID2) Immunogen Doses on Elicitation of Anti-HIV-1 Functional Fc-Effector Response to C1/C2 (Cluster A) Epitopes in Mice

“…For murine antibodies, IgG2a (equivalent to human IgG3), IgG2b (equivalent to human IgG1) and IgG3 are known to be involved in Fc-effector mechanisms [ 74 ]. In addition, both murine IgG2a and IgG3 have been shown to induce ADCC and generate IFNγ in the presence of human monocytic cells, indicating the Fc region of both isotypes are able to bind and activate human Fcγ receptors on human monocytes [ 75 ], IgG2a is thought to play the role of human IgG3 as it displays the highest affinities to FcγRIV, the primary receptor involved in ADCC in mice [ 76 ]. This is of particular importance for our studies since all ADCC measurements were carried out using human PBMCs [ 56 ] in an RFADCC assay know to heavily rely on monocytes [ 77 ].…”

SARS, SARS again, and MERS. Review of animal models of human respiratory syndromes caused by coronavirus infections

“…Учитывая, что хорьки продемонстрировали относительную восприимчивость к SARS-CoV, а также к некоторым другим респираторным инфекциям [25,26], на них были осуществлены и попытки воспроизведения патогенеза MERS-CoV. Однако интраназальное и интратрахеальное заражение хорьков MERS-CoV в дозе 10 6 TCID 50 не вызвало сероконверсии, а сам инфекционный вирус у животных не обнаружен [18].…”