Treatment with sofosbuvir attenuates the adverse neurodevelopmental consequences of Zika virus infection in infant rhesus macaques

Alejandra Medina; Rebecca Rusnak; Rebecca Richardson; Matthew G Zimmerman; Mehul Suthar; Nils Schoof; Zsofia Kovacs-Balint; Maud Mavigner; Mar Sanchez; Ann Chahroudi; Jessica Raper

doi:10.1016/j.jneuroim.2023.578148

Treatment with sofosbuvir attenuates the adverse neurodevelopmental consequences of Zika virus infection in infant rhesus macaques

J Neuroimmunol. 2023 Aug 15:381:578148. doi: 10.1016/j.jneuroim.2023.578148. Epub 2023 Jul 7.

Authors

Affiliations

¹ Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
² Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA; Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.
³ Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.
⁴ Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA; Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA.
⁵ Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA; Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA; Children's Healthcare of Atlanta, Atlanta, GA 30322, USA.
⁶ Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA; Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA. Electronic address: jraper@emory.edu.

PMID: 37451078
PMCID: PMC10528946 (available on 2024-08-15)
DOI: 10.1016/j.jneuroim.2023.578148

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.

Keywords: Antiviral; Cognitive function; Emotional reactivity; Motor function; Prophylaxis; Social behavior.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Animals
Antiviral Agents / therapeutic use
Macaca mulatta
Sofosbuvir / therapeutic use
Zika Virus Infection* / complications
Zika Virus Infection* / drug therapy
Zika Virus*

Substances

Sofosbuvir
Antiviral Agents

Abstract

Publication types

MeSH terms

Substances

Grants and funding