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

#### **Ashley E. Saver 1, Stephanie A. Crawford 1, Jonathan D. Joyce 2 and Andrea S. Bertke 2,\***


Received: 1 October 2019; Accepted: 13 November 2019; Published: 14 November 2019

**Abstract:** 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/sta ff. 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.

**Keywords:** Zika virus; ZIKV; virus host interactions; pathogenesis; MR766; guinea pig; subcutaneous; vaginal; sexual transmission; virus transmission
