Development of a Zika Virus Infection Model in Cynomolgus Macaques
Fusataka Koide1, Scott Goebel1, Beth Snyder1
1Department of Infectious Disease Research, Drug Development, Southern Research Institute, Frederick MD, USA.
Abstract:
Limited availability of Indian rhesus macaques (IRM) is a bottleneck to study Zika virus (ZIKV) pathogenesis and evaluation of appropriate control measures in non-human primates. To address these issues, we report here the Mauritian cynomolgus macaque (MCM) model for ZIKV infection. In brief, six MCMs (seronegative for Dengue and ZIKV) were subdivided into three cohorts with a male and female each and challenged with different doses of Asian [PRVABC59 (Puerto Rico) or FSS13025 (Cambodia)] or African (IBH30656) lineage ZIKV isolates. Clinical signs were monitored; and biological fluids (serum, saliva, and urine) and tissues (testes and brain) were assessed for viral load by quantitative reverse transcription polymerase chain reaction and neutralizing antibodies (Nab) by 50% Plaque Reduction Neutralization Test (PRNT50) at various times post-infection (p.i). PRVABC59 induced viremia detectable up to day 10, with peak viral load at 2-3 days p.i. An intermittent viremia spike was observed on day 30 with titers reaching 2.5 × 103 genomes/mL. Moderate viral load was observed in testes, urine and saliva. In contrast, FSS13025 induced viremia lasting only up to 6 days and detectable viral loads in testes but not in urine and saliva. Recurrent viremia was detected but at lower titers compare to PRVABC59. Challenge with either PRVABC59 or FSS13025 resulted in 100% seroconversion; with mean PRNT50 titers ranging from 597 to 5179. IBH30656 failed to establish infection in MCM suggesting that MCM are susceptible to infection with ZIKV isolates of the Asian lineage but not from Africa. Due to the similarity of biphasic viremia and Nab responses between MCM and IRM models, MCM could be a suitable alternative for evaluation of ZIKV vaccine and therapeutic candidates.
Insights
The Mauritian cynomolgus macaque (MCM) model effectively mimics Zika virus (ZIKV) infection, showing susceptibility to Asian ZIKV strains. This primate model is a promising alternative for evaluating ZIKV vaccines and therapeutics.
Area of Science:
- Virology
- Primate Models
- Infectious Diseases
Background:
- Limited availability of Indian rhesus macaques (IRM) hinders Zika virus (ZIKV) research.
- Development of alternative non-human primate models is crucial for ZIKV pathogenesis studies and control measure evaluation.
Purpose of the Study:
- To establish and characterize the Mauritian cynomolgus macaque (MCM) as a model for ZIKV infection.
- To assess MCM susceptibility to different ZIKV lineages and evaluate viral dynamics and immune responses.
Main Methods:
- Six ZIKV and Dengue-seronegative MCMs were challenged with Asian (PRVABC59, FSS13025) or African (IBH30656) ZIKV isolates.
- Viral load in biological fluids and tissues was quantified using RT-qPCR.
- Neutralizing antibody (Nab) responses were measured by 50% Plaque Reduction Neutralization Test (PRNT50).
Main Results:
- Asian ZIKV strains (PRVABC59, FSS13025) induced viremia, with PRVABC59 showing biphasic viremia up to 30 days post-infection.
- Moderate viral loads were detected in testes, urine, and saliva for PRVABC59, and in testes for FSS13025.
- All challenged MCMs seroconverted, developing robust Nab responses; African ZIKV strain IBH30656 did not establish infection.
Conclusions:
- Mauritian cynomolgus macaques are susceptible to Asian ZIKV lineages but not African ones.
- The MCM model exhibits biphasic viremia and Nab responses similar to IRMs, making it a suitable alternative for ZIKV vaccine and therapeutic candidate evaluation.
