Immunosuppression-induced Zika virus reactivation causes brain inflammation and behavioral deficits in mice

• Published in: iScience Vol. 27; no. 7; p. 110178
• Main Authors: Nogueira, Clara de O., Lopes da Silva, Mariana Oliveira, de Lima, Emanuelle V., Christoff, Raíssa Rilo, Gavino-Leopoldino, Daniel, Lemos, Felipe S., da Silva, Nicolas E., Da Poian, Andrea T., Assunção-Miranda, Iranaia, Figueiredo, Claudia P., Clarke, Julia R.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 19.07.2024; Elsevier
• Subjects: Immunology; Neuroscience; Virology; Neuroscience; Immunology; Virology
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2024.110178

Zika virus (ZIKV) is a neurotropic flavivirus that can persist in several tissues. The late consequences of ZIKV persistence and whether new rounds of active replication can occur, remain unaddressed. Here, we investigated whether neonatally ZIKV-infected mice are susceptible to viral reactivation in adulthood. We found that when ZIKV-infected mice are treated with immunosuppressant drugs, they present increased susceptibility to chemically induced seizures. Levels of subgenomic flavivirus RNAs (sfRNAs) were increased, relative to the amounts of genomic RNAs, in the brains of mice following immunosuppression and were associated with changes in cytokine expression. We investigated the impact of immunosuppression on the testicles and found that ZIKV genomic RNA levels are increased in mice following immunosuppression, which also caused significant testicular damage. These findings suggest that ZIKV can establish new rounds of active replication long after acute stages of disease, so exposed patients should be monitored to ensure complete viral eradication. [Display omitted] •Immunosuppression late after ZIKV infection increases seizures in mice•Immunosuppression leads to viral replication late after ZIKV infection•Immunosuppression increases ZIKV sfRNA levels late after ZIKV infection•Immunosuppression leads to testicular damage late after ZIKV infection Neuroscience; Immunology; Virology