The use of mice lacking type I or both type I and type II interferon responses in research on hemorrhagic fever viruses. Part 1: Potential effects on adaptive immunity and response to vaccination

• Published in: Antiviral research Vol. 174; p. 104703
• Main Authors: Clarke, Elizabeth C., Bradfute, Steven B.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.02.2020
• Subjects: Hemorrhagic fever viruses; Immune responses; Interferon-deficient mice; Type I IFNs; Type II IFNs; Vaccines; Hemorrhagic fever viruses; Type I IFNs; Type II IFNs; Vaccines; Immune responses; Interferon-deficient mice
• ISSN: 0166-3542; 1872-9096
• DOI: 10.1016/j.antiviral.2019.104703

For more than 20 years, researchers have used laboratory mice lacking type I or both type I and type II interferon (IFN) responses to study viruses that cause hemorrhagic fever (HF) in humans. Whereas immunocompetent mice do not become ill when infected with Ebola, Lassa, dengue and other HF viruses, IFN-deficient mice typically develop severe or fatal disease when inoculated with these pathogens. The ease of employment of these “mouse models” has led to their extensive use in biocontainment laboratories to assess the efficacy of novel vaccines, often without consideration of whether adaptive immune responses in IFN-deficient mice accurately mirror those in humans. Failure to consider these questions may lead to inappropriate expectations of the predictive value of mouse experiments. In two invited articles, we investigate this question. This paper examines how the lack of type I or both type I and type II IFN signaling may affect the development of adaptive immune responses in mice and the outcome of vaccine studies. A second article reviews the published literature on the use of IFN-deficient mice for the assessment of novel vaccines against HF viruses. •Interferons (IFNs) are important antiviral cytokines.•Mice lacking type I or II IFNs are susceptible to many hemorrhagic fever viruses and are used in vaccine studies.•Mice lacking IFN responses can have altered adaptive immune responses after vaccination compared to wild-type mice.•Vaccine studies using IFN-deficient mice must determine if adaptive immunity is altered to verify experimental validity.•The use of transient or cell-specific IFN depletion should be considered as alternatives to knockout mice.