Congenital Zika Virus Infection in Immunocompetent Mice Causes Postnatal Growth Impediment and Neurobehavioral Deficits

A small percentage of babies born to Zika virus (ZIKV)-infected mothers manifest severe defects at birth, including microcephaly. Among those who appeared healthy at birth, there are increasing reports of postnatal growth or developmental defects. However, the impact of congenital ZIKV infection in postnatal development is poorly understood. Here, we report that a mild congenital ZIKV-infection in pups born to immunocompetent pregnant mice did not display apparent defects at birth, but manifested postnatal growth impediments and neurobehavioral deficits, which include reduced locomotor and cognitive deficits that persisted into adulthood. We found that the brains of these pups were smaller, had a thinner cortical layer 1, displayed increased astrogliosis, decreased expression of microcephaly- and neuron development- related genes, and increased pathology as compared to mock-infected controls. In summary, our results showed that even a mild congenital ZIKV infection in immunocompetent mice could lead to postnatal deficits, providing definitive experimental evidence for a necessity to closely monitor postnatal growth and development of presumably healthy human infants, whose mothers were exposed to ZIKV infection during pregnancy

Chronic Exposure to West Nile Virus Leads to Neuroinvasive-Like Syndrome in Mice (P5.146)

Objective: The objective was to develop a mouse model of slowly progressing neuroinvasive West Nile virus (WNV) disease that could mimic human condition and help determine the neuropathologic basis of WNV infection. Background: WNV may cause a significant neuroinvasive disease involving the brain and/or spinal cord. Neuroinvasive WNV infection has a high mortality and many who recover present with long-term deficits, including weakness, fatigue, and cognitive problems. Some of these symptoms are also observed after WNV fever. The exact reasons for lingering symptoms following various clinical presentations of WNV infection remain obscure. This hinders development of specific treatments for neurologic sequelae of WNV infection. Design/Methods: Seven week old Brainbow-PV Cre mice were treated with a single sub-acute dose (20–50 PFU) of WNV via IP injection (at USM). Mice were kept up to 2, 4 and 6 months post-infection, followed by behavior testing, sacrifice, immunohistochemical and Western blot analyses. Also, cerebellar and spinal cord tissue was processed for total mRNA extraction and gene expression profiling (UMMC’s Molecular and Genomics Facility). Results: WNV treated mice showed a significant decrease in grip strength at 4 and 6 months post-infection with no balance or motor coordination deficits. The Western blot data revealed unchanged levels of cerebellar neuronal marker proteins at all age intervals; however, astrocytic S100B levels were altered at 2, 4 and 6 months as compared to mock treated animals. The expression profiles of several genes in the cerebellar and spinal cord tissue was significantly altered in WNV treated group; the Toll-like receptor signaling and the cytokine/chemokine signaling were more severely affected in the spinal cord than cerebellum. Conclusions: Alterations in the expression of astrocyte specific genes, which are members of and/or are related to the above pathways need further analysis, which may reveal new targets or potential biomarkers of WNV infection and assist in developing novel therapies

Congenital Zika Virus Infection in Immunocompetent Mice Causes Postnatal Growth Impediment and Neurobehavioral Deficits

A small percentage of babies born to Zika virus (ZIKV)-infected mothers manifest severe defects at birth, including microcephaly. Among those who appeared healthy at birth, there are increasing reports of postnatal growth or developmental defects. However, the impact of congenital ZIKV infection in postnatal development is poorly understood. Here, we report that a mild congenital ZIKV-infection in pups born to immunocompetent pregnant mice did not display apparent defects at birth, but manifested postnatal growth impediments and neurobehavioral deficits, which include reduced locomotor and cognitive deficits that persisted into adulthood. We found that the brains of these pups were smaller, had a thinner cortical layer 1, displayed increased astrogliosis, decreased expression of microcephaly- and neuron development- related genes, and increased pathology as compared to mock-infected controls. In summary, our results showed that even a mild congenital ZIKV infection in immunocompetent mice could lead to postnatal deficits, providing definitive experimental evidence for a necessity to closely monitor postnatal growth and development of presumably healthy human infants, whose mothers were exposed to ZIKV infection during pregnancy