Experimental Zika virus infection of Jamaican fruit bats (Artibeus jamaicensis) and possible entry of virus into brain via activated microglial cells.

The emergence of Zika virus (ZIKV) in the New World has led to more than 200,000 human infections. Perinatal infection can cause severe neurological complications, including fetal and neonatal microcephaly, and in adults there is an association with Guillain-Barre syndrome (GBS). ZIKV is transmitted to humans by Aedes sp. mosquitoes, yet little is known about its enzootic cycle in which transmission is thought to occur between arboreal Aedes sp. mosquitos and non-human primates. In the 1950s and 60s, several bat species were shown to be naturally and experimentally susceptible to ZIKV with acute viremia and seroconversion, and some developed neurological disease with viral antigen detected in the brain. Because of ZIKV emergence in the Americas, we sought to determine susceptibility of Jamaican fruit bats (Artibeus jamaicensis), one of the most common bats in the New World. Bats were inoculated with ZIKV PRVABC59 but did not show signs of disease. Bats held to 28 days post-inoculation (PI) had detectable antibody by ELISA and viral RNA was detected by qRT-PCR in the brain, saliva and urine in some of the bats. Immunoreactivity using polyclonal anti-ZIKV antibody was detected in testes, brain, lung and salivary glands plus scrotal skin. Tropism for mononuclear cells, including macrophages/microglia and fibroblasts, was seen in the aforementioned organs in addition to testicular Leydig cells. The virus likely localized to the brain via infection of Iba1(+) macrophage/microglial cells. Jamaican fruit bats, therefore, may be a useful animal model for the study of ZIKV infection. This work also raises the possibility that bats may have a role in Zika virus ecology in endemic regions, and that ZIKV may pose a wildlife disease threat to bat populations. Author summary The rapid spread of Zika virus through a naive population in the Americas resulted in novel and severe disease manifestations, including fetal and neonatal microcephaly, and GBS. These disease complications make understanding the pathology and ecology of ZIKV a priority. Captive Jamaican fruit bats were challenged with ZIKV to determine their susceptibility, to assess whether bats may play a role in virus ecology, and if they might serve as an animal model to better understand ZIKV pathophysiology. The bats became acutely infected and mounted an antibody response. Three terminally euthanized inoculated bats had antibody titers of 3200, 28 days PI. Evidence of virus replication and associated pathologies were found in the brain, testes, lungs and salivary glands of some of the inoculated bats. The virus showed predilection for mononuclear cells, including resident Iba1(+) macrophage/microglial cells, and Leydig cells. With no discernible disruption to the blood brain barrier nor distribution of viral antigen indicative of circumeventricular neuroinvasion, microglia cells may be a possible route of entry of ZIKV into brains of bats. Further investigations are needed to determine the mechanisms of neuroinvasion of ZIKV in bats, further determine feasibility of bats as an alternative animal-model for congenital Zika syndrome, and what role bats might play in ZIKV viral ecology.