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ZIKV Demonstrates Minimal Pathologic Effects and Mosquito Infectivity in Viremic Cynomolgus Macaques
Sasha R Azar1,2,3, Shannan L Rossi4,5,6,7, Sherry H Haller8
1Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA. srazar@utmb.edu.
Abstract:
To evaluate the effects of ZIKV infection on non-human primates (NHPs), as well as to investigate whether these NHPs develop sufficient viremia to infect the major urban vector mosquito, Aedes aegypti, four cynomolgus macaques (Macaca fascicularis) were subcutaneously infected with 5.0 log10 focus-forming units (FFU) of DNA clone-derived ZIKV strain FSS13025 (Asian lineage, Cambodia, 2010). Following infection, the animals were sampled (blood, urine, tears, and saliva), underwent daily health monitoring, and were exposed to Ae. aegypti at specified time points. All four animals developed viremia, which peaked 3⁻4 days post-infection at a maximum value of 6.9 log10 genome copies/mL. No virus was detected in urine, tears, or saliva. Infection by ZIKV caused minimal overt disease: serum biochemistry and CBC values largely fell within the normal ranges, and cytokine elevations were minimal. Strikingly, the minimally colonized population of Ae. aegypti exposed to viremic animals demonstrated a maximum infection rate of 26% during peak viremia, with two of the four macaques failing to infect a single mosquito at any time point. These data indicate that cynomolgus macaques may be an effective model for ZIKV infection of humans and highlights the relative refractoriness of Ae. aegypti for ZIKV infection at the levels of viremia observed.
Insights
Zika virus (ZIKV) infection in cynomolgus macaques caused minimal disease but led to viremia capable of infecting mosquitoes. However, the infection rate in Aedes aegypti mosquitoes was low, suggesting macaques are a viable ZIKV model but mosquitoes are relatively refractory.
Area of Science:
- Virology
- Infectious Diseases
- Primate Models
Background:
- Zika virus (ZIKV) poses a significant public health threat.
- Understanding ZIKV pathogenesis in animal models is crucial for vaccine and therapeutic development.
- Non-human primates (NHPs) are being investigated as models for ZIKV infection.
Purpose of the Study:
- To evaluate ZIKV infection effects in cynomolgus macaques (Macaca fascicularis).
- To determine if NHPs develop sufficient viremia to infect the urban vector mosquito, Aedes aegypti.
- To assess ZIKV disease severity and transmission potential in this NHP model.
Main Methods:
- Four cynomolgus macaques were infected with ZIKV (FSS13025 strain).
- Animals were monitored daily, with blood, urine, tears, and saliva sampled.
- NHPs were exposed to Aedes aegypti mosquitoes at specified time points post-infection.
Main Results:
- All macaques developed viremia, peaking at 3-4 days post-infection (max 6.9 log10 genome copies/mL).
- No ZIKV was detected in urine, tears, or saliva.
- Mosquitoes exposed during peak viremia showed a maximum infection rate of 26%; two macaques did not infect any mosquitoes.
Conclusions:
- Cynomolgus macaques serve as a potential model for human ZIKV infection.
- ZIKV infection in these macaques caused minimal overt disease.
- Aedes aegypti mosquitoes demonstrated relative refractoriness to ZIKV infection at observed viremia levels.
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