Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Nov 13;228(Suppl 7):S548-S553.
doi: 10.1093/infdis/jiad226.

Pathogenicity of Lloviu and Bombali Viruses in Type I Interferon Receptor Knockout Mice

Paige Fletcher  1 , Friederike Feldmann  2 , Ayato Takada  3 , Nicholas A Crossland  4   5 , Adam J Hume  4   6 , César Albariño  7 , Gábor Kemenesi  8   9 , Heinz Feldmann  1 , Elke Mühlberger  4   6 , Andrea Marzi  1
Affiliations

Pathogenicity of Lloviu and Bombali Viruses in Type I Interferon Receptor Knockout Mice

Paige Fletcher et al. J Infect Dis. .

Abstract

Type I interferon receptor knockout (IFNAR-/-) mice are not able to generate a complete innate immune response; therefore, these mice are often considered to assess the pathogenicity of emerging viruses. We infected IFNAR-/- mice with a low or high dose of Lloviu virus (LLOV) or Bombali virus (BOMV) by the intranasal (IN) or intraperitoneal (IP) route and compared virus loads at early and late time points after infection. No signs of disease and no viral RNA were detected after IN infection regardless of LLOV dose. In contrast, IP infections resulted in increased viral loads in the high-dose LLOV and BOMV groups at the early time point. The low-dose LLOV and BOMV groups achieved higher viral loads at the late time point. However, there was 100% survival in all groups and no signs of disease. In conclusion, our results indicate a limited value of the IFNAR-/- mouse model for investigation of the pathogenicity of LLOV and BOMV.

Keywords: Cuevavirus; Ebolavirus; emerging filovirus; intranasal infection; intraperitoneal infection.

PubMed Disclaimer

Conflict of interest statement

Potential conflicts of interest . All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1.
Figure 1.
Intranasal LLOV infection. IFNAR−/− mice (n = 10) were infected intranasally with either 100 (low-dose) or 100 000 (high-dose) TCID50 of LLOV, RESTV, or EBOV. At 7 days postinfection, 4 mice in each group were euthanized for sample analysis. A, Viral RNA in blood, lung, liver, and spleen. Geometric mean and standard deviation are depicted. B, Body weight changes over time. C, LLOV GP-specific IgG in serum at study end (day 28). B, C Mean and standard error of the mean are depicted. Statistical significance is indicated as ****P < .0001. Abbreviations: EBOV, Ebola virus; GP, glycoprotein; IFNAR−/−, type I interferon receptor knockout; IgG, immunoglobulin G; LLOV, Lloviu virus; RESTV, Reston virus; TCID50, 50% tissue culture infectious dose; wt, wild type.
Figure 2.
Figure 2.
Intraperitoneal infections of emerging filoviruses. IFNAR−/− mice were infected intraperitoneally with either 100 (low-dose) TCID50 EBOV, rgLLOV, wtLLOV, or BOMV, or 100 000 (high-dose) TCID50 of rgLLOV, wtLLOV, BOMV, or RESTV. At 3 or 6 days postinfection, 4 mice in each group were euthanized for sample analysis. A and D, Viral RNA in blood, liver, and spleen. B and E, Body weight changes over time. C, LLOV GP-specific or (F) BOMV GP-specific IgG in serum at study end (day 28). A, C, D, F Geometric mean and geometric standard deviation are depicted. B, E Mean and standard error of the mean are depicted. Statistical significance indicated as ****P < .0001. Abbreviations: BOMV, Bombali virus; EBOV, Ebola virus; FFU, focus-forming unit; GP, glycoprotein; IFNAR−/−,type I interferon receptor knockout; IgG, immunoglobulin G; RESTV, Reston virus; rgLLOV, reverse genetics Lloviu virus; TCID50, 50% tissue culture infectious dose; wtLLOV, wild-type Lloviu virus.
See this image and copyright information in PMC

References

    1. Kuhn JH, Amarasinghe GK, Basler CF, et al. . ICTV virus taxonomy profile: filoviridae. J Gen Virol 2019; 100:911–2. - PMC - PubMed
    1. Marzi A, Banadyga L. Ebola virus (filoviridae). In: Bamford DH, Zuckerman M, eds. Encyclopedia of virology. 4th ed. Vol. 2. 2021:232–44.
    1. Burk R, Bollinger L, Johnson JC, et al. . Neglected filoviruses. FEMS Microbiol Rev 2016; 40:494–519. - PMC - PubMed
    1. McMullan LK, Flint M, Jenks MH, et al. . Characterization of Bombali virus, a new bat filovirus. SSRN, doi: 10.2139/ssrn.4035855, 15February2022, preprint: not peer reviewed. - DOI
    1. Negredo A, Palacios G, Vazquez-Moron S, et al. . Discovery of an ebolavirus-like filovirus in Europe. PLoS Pathog 2011; 7:e1002304. - PMC - PubMed

Publication types

Substances