Three Immunocompetent Small Animal Models That Do Not Support Zika Virus Infection

Abstract

Zika virus (ZIKV) is a mosquito-borne flavivirus that is primarily transmitted to humans through the bite of an infected mosquito. ZIKV causes disease in infected humans with added complications of Guillain-Barré syndrome and birth defects in infants born to mothers infected during pregnancy. There are several large immunocompetent animal models for ZIKV including non-human primates (NHPs). NHP models closely reflect human infection; however, due to sample size restrictions, investigations into the effects of transmission route and the impacts on disease dynamics have been understudied. Mice have been widely used for modeling ZIKV infection, yet there are few ZIKV-susceptible immunocompetent mouse models and none of these have been used to investigate sexual transmission. In an effort to identify a small immunocompetent animal model to characterize sexual transmission of ZIKV, we attempt experimental infection of multimammate mice, New Zealand white rabbits, and Hartley guinea pigs. The multimammate mouse is the natural reservoir of Lassa fever virus and has been identified to harbor other human pathogens. Likewise, while NZW rabbits are susceptible to West Nile virus, they have not yet been examined for their susceptibility to infection with ZIKV. Guinea pigs have been successfully used as models for ZIKV infection, but only in immunocompromised life stages (young or pregnant). Here, it was found that the multimammate mouse and New Zealand White (NZW) rabbits are not susceptible ZIKV infection as determined by a lack viral RNA in tissues and fluids collected. Sexually mature male Hartley guinea pigs were inoculated subcutaneously and by mosquito bite, but found to be refractory to ZIKV infection, contrary to findings of other studies in young and pregnant guinea pigs. Interestingly, here it is shown that adult male guinea pigs are not susceptible to ZIKV infection, even when infected by natural route (e.g., mosquito bite). Although a new small animal model for the sexual transmission for ZIKV was not established through this study, these findings provide information on outbred animal species that are not permissive to infection (NZW rabbits and multimammate mice) and new information surrounding limitations of a previously established animal model (guinea pigs).

Nanoluciferase Reporter Zika Viruses as Tools for Assessing Infection Kinetics and Antibody Potency

“…Finally, using nLuc-ZIKV reporter to perform an in vivo infection study in immunecompetent guinea pigs, we showed that a subset of the guinea pigs inoculated with nLuc-ZIKV displayed increased bioluminescence on PID 3 compared to sham controls (Figure 5). The variability in response depending on viral strain, age, dose, and laboratory where the study was performed has been reported in this species [16,[27][28][29] and is also likely the case in the human population. Using these variants in animal models highly susceptible to ZIKV infection, such as mouse knockout strains lacking interferon responses, may provide a more robust model for studying this infection using live imaging.…”

The Susceptibility of Chickens to Zika Virus: A Comprehensive Study on Age-Dependent Infection Dynamics and Host Responses

“…ZIKV is detectable by RT-PCR in the spleen, the brain, and several other tissues [ 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 ]. In contrast, non-susceptible species have little or no virus detectable in their blood during the first three days after inoculation, and ZIKV is not detectable in their tissues [ 64 , 65 , 66 ].…”