Route of Infection Influences Zika Virus Shedding in a Guinea Pig Model.

Due to the recent epidemic of Zika virus (ZIKV) infection and resulting sequelae, as well as concerns about both the sexual and vertical transmission of the virus, renewed attention has been paid to the pathogenesis of this unique arbovirus. Numerous small animal models have been used in various ZIKV pathogenicity studies, however, they are often performed using immunodeficient or immunosuppressed animals, which may impact disease progression in a manner not relevant to immunocompetent humans. The use of immunocompetent animal models, such as macaques, is constrained by small sample sizes and the need for specialized equipment/staff. Here we report the establishment of ZIKV infection in an immunocompetent small animal model, the guinea pig, using both subcutaneous and vaginal routes of infection to mimic mosquito-borne and sexual transmission. Guinea pigs developed clinical signs consistent with mostly asymptomatic and mild disease observed in humans. We demonstrate that the route of infection does not significantly alter viral tissue tropism but does impact mucosal shedding mechanics. We also demonstrate persistent infection in sensory and autonomic ganglia, identifying a previously unrecognized niche of viral persistence that could contribute to viral shedding in secretions. We conclude that the guinea pig represents a useful and relevant model for ZIKV pathogenesis.

Zika Virus Persistently and Productively Infects Primary Adult Sensory Neurons In Vitro.

Zika virus (ZIKV) has recently surged in human populations, causing an increase in congenital and Guillain-Barré syndromes. While sexual transmission and presence of ZIKV in urine, semen, vaginal secretions, and saliva have been established, the origin of persistent virus shedding into biological secretions is not clear. Using a primary adult murine neuronal culture model, we have determined that ZIKV persistently and productively infects sensory neurons of the trigeminal and dorsal root ganglia, which innervate glands and mucosa of the face and the genitourinary tract, respectively, without apparent injury. Autonomic neurons that innervate these regions are not permissive for infection. However, productive ZIKV infection of satellite glial cells that surround and support sensory and autonomic neurons in peripheral ganglia results in their destruction. Persistent infection of sensory neurons, without affecting their viability, provides a potential reservoir for viral shedding in biological secretions for extended periods of time after infection. Furthermore, viral destruction of satellite glial cells may contribute to the development of Guillain-Barré Syndrome via an alternative mechanism to the established autoimmune response.

Immunocontraception for Animals: Current Status and Future Perspective.

An alternative to surgical sterilization for fertility control of animals (wild, zoo, farm, and domestic) is needed to prevent problems related to overpopulation, including culling and relocation. A PubMed and Google Scholar database search was conducted using the keywords 'contraceptive vaccine animals,' 'immunocontraception animals,' 'non-surgical sterilization animals,' 'PZP vaccine,' and 'GnRH vaccine.' The searches from 1972 to 2015 yielded over 1500 publications. These articles were read, and 375 were selected for detailed analysis. Articles referenced in these publications were also thoroughly examined. PZP and GnRH contraceptive vaccines (CVs) have been extensively investigated for fertility control of wild, zoo, farm, and domestic animal populations. Both vaccines have shown tremendous success with PZP vaccines taking the lead. Novel technologies and targets are being developed to improve existing vaccines and generate second-generation CVs. Single-shot vaccines, which can be delivered remotely, will greatly advance the field of immunocontraception for animal use with potential human application.