Treatment with sofosbuvir attenuates the adverse neurodevelopmental consequences of Zika virus infection in infant rhesus macaques
Alejandra Medina1, Rebecca Rusnak1, Rebecca Richardson1
1Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
Insights
Postexposure prophylaxis with sofosbuvir (SOF) mitigated neurodevelopmental and behavioral changes in infant rhesus macaques infected with Zika virus (ZIKV). This antiviral treatment offers potential for ameliorating long-term effects of early ZIKV exposure.
Area of Science:
- Neuroscience
- Virology
- Pharmacology
Background:
- Zika virus (ZIKV) infection in infancy poses significant risks to brain development, leading to persistent behavioral deficits.
- Rhesus macaque (RM) models are crucial for understanding ZIKV's impact on neurodevelopment.
- Investigating postexposure prophylaxis is vital for mitigating ZIKV-induced neurodevelopmental consequences.
Purpose of the Study:
- To evaluate the efficacy of postexposure sofosbuvir (SOF) treatment in alleviating neurodevelopmental and behavioral impairments caused by early-life Zika virus infection in a rhesus macaque model.
Main Methods:
- Three infant rhesus macaques received a 14-day course of sofosbuvir (15 mg/kg) starting 3 days post-ZIKV infection.
- Longitudinal monitoring for one year assessed neurodevelopmental, behavioral, and cognitive outcomes.
- Viral load in blood was monitored to assess viral clearance.
Main Results:
- Postexposure SOF treatment significantly mitigated neurodevelopmental, behavioral, and cognitive deficits observed in ZIKV-infected infant RMs.
- SOF treatment did not accelerate viral clearance from the bloodstream.
- Despite improvements, some neurodevelopmental abnormalities may persist.
Conclusions:
- Sofosbuvir (SOF) as a postexposure prophylaxis demonstrates potential in ameliorating some long-term neurodevelopmental abnormalities following early postnatal Zika virus (ZIKV) infection.
- Antiviral therapy may offer a therapeutic window to mitigate ZIKV's detrimental effects on infant brain development.
- Further research is warranted to fully understand the scope and limitations of SOF in managing ZIKV-related neurodevelopmental sequelae.
Abstract:
Zika virus (ZIKV) infection during infancy in a rhesus macaque (RM) model negatively impacts brain development resulting in long-term behavioral alterations. The current study investigated whether postexposure prophylaxis could alleviate these negative neurodevelopmental consequences. Three RM infants received a 14-day course of sofosbuvir (SOF; 15 mg/kg p.o.) treatment starting at 3 days post-infection with a Puerto Rican strain of ZIKV (PRVABC59) and were then monitored longitudinally for one year. In contrast to ZIKV-infected infant RMs who did not receive SOF, postexposure SOF treatment mitigated the neurodevelopmental, behavioral and cognitive changes seen after postnatal ZIKV infection even while not accelerating viral clearance from the blood. These data suggest that antiviral treatment may help ameliorate some, but not all, of the neurodevelopmental abnormalities associated with early postnatal ZIKV infection.
