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

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).

Hematologic and serum biochemistry reference intervals using defined ASCVP methodology for laboratory natal multimammate mice (Mastomys natalensis)

Complete blood count, serum chemistry values, and biological reference intervals were compared between two age groups (34–49 and 84–120 days old) of healthy male and female laboratory raised natal multimammate mice ( Mastomys natalensis). Blood was collected via cardiocentesis under isoflurane anesthesia. Data sets of machine automated complete blood counts and clinical chemistries were analyzed. Significant differences between sex and age groups of the data sets were defined. The baseline hematologic and serum biochemistry values described here can improve interpretation of laboratory research using natal multimammate mice.

Comparing arenavirus infection patterns in experimentally and naturally infected rodent hosts

Infectious diseases of wildlife are typically studied using data on antibody and pathogen presence/level. In order to interpret these data, it is necessary to know the course of antibodies and pathogen presence/levels after infection. Such data are typically collected using experimental infection studies in which host individuals are inoculated in the laboratory and sampled over an extended period, but because laboratory conditions are controlled and much less variable than natural conditions, the immune response and pathogen dynamics may differ. Here, we compared Morogoro arenavirus infection patterns between naturally and experimentally infected multimammate mice (Mastomys natalensis). Longitudinal samples were collected during three months of bi-weekly trapping in Morogoro, Tanzania, and antibody titer and viral RNA presence were determined to assess whether the natural temporal patterns are similar to those previously observed in the laboratory. A good match with laboratory data was found for 52% of naturally infected individuals, while most of the mismatches can be explained by the presence of chronically infected individuals (35%), maternal antibodies (10%) and an antibody detection limit (25%). These results suggest that while laboratory data are useful for interpreting field samples, there can still be differences due to conditions that were not tested in the laboratory.Important noticeThis is a pre-print version of the manuscript, made available through bioRxiv.org. Note that this manuscript has not yet been peer-reviewed, and has been submitted to a peer-reviewed journal.

No evidence for avoidance of black rat scent by the presumably less competitive Natal multimammate mouse in a choice experiment

In Africa, indigenous multimammate mice (Mastomys natalensis) only appear to live commensally in houses when invasive black rats (Rattus rattus) are absent, yet little is known about the underlying mechanism. Avoidance through smell may cause the absence of M. natalensis from areas occupied by R. rattus, but this hypothesis has not yet been tested. We conducted a Y-maze choice experiment where 15 M. natalensis were offered a choice between corridors containing conspecific scent, R. rattus scent, and a control scent. Residence time in the R. rattus corridor was greater than that in the control corridor but equal to that in the M. natalensis corridor, suggesting that multimammate mice do not actively avoid the scent of their invasive competitor.

Evaluation of short-, mid- and long-term effects of toe clipping on a wild rodent

Context Toe clipping is a widely used method for permanent marking of small mammals, but its effects are not well known, despite the ethical and scientific implications. Most studies do not find any clear effects, but there is some indication that toe clipping can affect survival in specific cases. Although effects on survival are arguably the most important, more subtle effects are also plausible, yet very few studies have included body condition and none has investigated effects on mobility. Aims We analysed the effects of toe clipping on free-living Mastomys natalensis, a common, morphologically and behaviourally intermediate small rodent. Methods Using a 17-year capture–mark–recapture dataset, we compared movement, body weight and survival between newly and previously clipped animals, and tested whether any of these parameters correlated with the number of clipped toes. Key results No evidence for a correlation between total number of clips and any of the variables was found. Newly clipped animals had a slightly smaller weight change and larger travel distance than did those that were already clipped, and we show that this is most likely due to stress caused by being captured, clipped and handled for the first time rather than to the actual clipping. Conclusions The combination of trapping, handling and marking has a detectable effect on multimammate mice; however, there is no evidence for a clear effect of toe clipping. Implications Our study suggests a re-evaluation of ethical guidelines on small-mammal experiments, so as to reach a rational, fact-based decision on which marking method to use.