Modeling Arboviral Infection in Mice Lacking the Interferon Alpha/Beta Receptor

Abstract

Arboviruses are arthropod-borne viruses that exhibit worldwide distribution and are a constant threat, not only for public health but also for wildlife, domestic animals, and even plants. To study disease pathogenesis and to develop efficient and safe therapies, the use of an appropriate animal model is a critical concern. Adult mice with gene knockouts of the interferon α/β (IFN-α/β) receptor (IFNAR(−/−)) have been described as a model of arbovirus infections. Studies with the natural hosts of these viruses are limited by financial and ethical issues, and in some cases, the need to have facilities with a biosafety level 3 with sufficient space to accommodate large animals. Moreover, the number of animals in the experiments must provide results with statistical significance. Recent advances in animal models in the last decade among other gaps in knowledge have contributed to the better understanding of arbovirus infections. A tremendous advantage of the IFNAR(−/−) mouse model is the availability of a wide variety of reagents that can be used to study many aspects of the immune response to the virus. Although extrapolation of findings in mice to natural hosts must be done with care due to differences in the biology between mouse and humans, experimental infections of IFNAR(−/−) mice with several studied arboviruses closely mimics hallmarks of these viruses in their natural host. Therefore, IFNAR(−/−) mice are a good model to facilitate studies on arbovirus transmission, pathogenesis, virulence, and the protective efficacy of new vaccines. In this review article, the most important arboviruses that have been studied using the IFNAR(−/−) mouse model will be reviewed.

Inhibition of Orbivirus Replication by Aurintricarboxylic Acid

“…Even if it has been shown that ATA has in vitro inhibitory activity against multiple RNA or DNA viruses [ 35 , 45 , 46 , 47 , 48 , 51 , 53 , 54 , 55 , 56 , 57 , 58 ], its antiviral efficacy in in vivo models has not been demonstrated [ 58 ], and there is a limited number of studies showing the effect of ATA in vivo [ 41 , 59 , 60 ]. Therefore, prior to conducting antiviral experiments in IFNAR (−/−) mice, a well-accepted mouse model to study BTV and AHSV infections [ 61 , 62 ], the effect of ATA in this animal model was assessed. For that, three groups of animals were treated daily for eight days with 600 µg of ATA diluted in PBS, DMSO diluted in PBS, or PBS.…”

Heterologous Combination of ChAdOx1 and MVA Vectors Expressing Protein NS1 as Vaccination Strategy to Induce Durable and Cross-Protective CD8+ T Cell Immunity to Bluetongue Virus

“…Type I interferon receptor defective mice (IFNAR (-/-)) on a 129 Sv/Ev background [ 42 ], and sheep (Spanish “Churra” sheep breed), were used for the studies. Mice and sheep were housed under pathogen-free conditions and allowed to acclimatize to the biosafety level 3 (BSL3) animal facilities at the Animal Health Research Center (INIA-CISA), Madrid, before use.…”

A protective bivalent vaccine against Rift Valley fever and bluetongue

“…Immune responses induced by dual MVA against proteins of RVFV and BTV in mice A number of experimental vaccines for BTV and RVFV have been previously studied in the mouse model based on IFNAR (−/−) mice [22][23][24][25][26][27][28] . Although extrapolation of findings in mice to natural hosts must be done with care due to differences in the biology between mouse and ruminants, experimental infections of IFNAR (−/−) mice with several studied arboviruses, such as BTV and RVFV closely mimics hallmarks of these viruses in their natural host 29 .…”