Related Experiment Video
Updated: Aug 27, 2025
Evaluation of Zika Virus-specific T-cell Responses in Immunoprivileged Organs of Infected Ifnar1-/- Mice
Published on: October 17, 2018
Mucosal Responses to Zika Virus Infection in Cynomolgus Macaques
Neil Berry1, Monja Stein2, Deborah Ferguson1
1Division of Infectious Disease Diagnostics, National Institute for Biological Standards and Control (NIBSC), Potters Bar EN6 3QC, UK.
Abstract:
Zika virus (ZIKV) cases continue to be reported, and no vaccine or specific antiviral agent has been approved for the prevention or treatment of infection. Though ZIKV is primarily transmitted by mosquitos, cases of sexual transmission and prolonged viral RNA presence in semen have been reported. In this observational study, we report the mucosal responses to sub-cutaneous and mucosal ZIKV exposure in cynomolgus macaques during acute and late chronic infection. Subcutaneous challenge induced a decrease in the growth factor VEGF in colorectal and cervicovaginal tissues 100 days post-challenge, in contrast to the observed increase in these tissues following vaginal infection. This different pattern was not observed in the uterus, where VEGF was upregulated independently of the challenge route. Vaginal challenge induced a pro-inflammatory profile in all mucosal tissues during late chronic infection. Similar responses were already observed during acute infection in a vaginal tissue explant model of ex vivo challenge. Non-productive and productive infection 100 days post-in vivo vaginal challenge induced distinct proteomic profiles which were characterized by further VEGF increase and IL-10 decrease in non-infected animals. Ex vivo challenge of mucosal explants revealed tissue-specific modulation of cytokine levels during the acute phase of infection. Mucosal cytokine profiles could represent biosignatures of persistent ZIKV infection.
Insights
Zika virus (ZIKV) infection impacts mucosal tissues differently depending on exposure route. Vaginal ZIKV exposure causes inflammation and distinct proteomic changes, suggesting mucosal cytokine profiles may indicate persistent infection.
Area of Science:
- Virology
- Immunology
- Infectious Diseases
Background:
- Zika virus (ZIKV) continues to be reported globally, with no approved vaccines or antiviral treatments.
- While primarily mosquito-borne, ZIKV exhibits sexual transmission and prolonged presence in semen.
- Understanding mucosal immune responses is crucial for managing ZIKV infection.
Purpose of the Study:
- To investigate mucosal immune responses to Zika virus (ZIKV) following subcutaneous and mucosal exposure in cynomolgus macaques.
- To characterize tissue-specific changes and proteomic profiles during acute and chronic ZIKV infection.
- To explore the potential of mucosal cytokine profiles as biomarkers for persistent ZIKV infection.
Main Methods:
- Observational study involving subcutaneous and vaginal ZIKV challenge in cynomolgus macaques.
- Analysis of growth factor VEGF and cytokine profiles in colorectal, cervicovaginal, and uterine tissues at 100 days post-challenge.
- Ex vivo challenge of mucosal explants to assess acute-phase immune responses.
- Proteomic analysis to differentiate between productive and non-productive infections.
Main Results:
- Subcutaneous ZIKV challenge decreased VEGF in colorectal and cervicovaginal tissues, while vaginal challenge increased it.
- VEGF was upregulated in the uterus irrespective of the challenge route.
- Vaginal ZIKV challenge induced a pro-inflammatory profile in mucosal tissues during late chronic infection.
- Distinct proteomic profiles were observed in non-productive versus productive infections, with altered VEGF and IL-10 levels.
- Ex vivo challenge revealed tissue-specific cytokine modulation during the acute phase.
Conclusions:
- Mucosal immune responses to ZIKV are route-dependent, with significant differences observed between subcutaneous and vaginal exposure.
- Vaginal ZIKV infection elicits a pro-inflammatory response and distinct proteomic signatures, particularly in later stages.
- Mucosal cytokine profiles show potential as diagnostic biomarkers for identifying persistent ZIKV infection.
More Related Videos
09:18Modelling Zika Virus Infection of the Developing Human Brain In Vitro Using Stem Cell Derived Cerebral Organoids
Published on: September 19, 2017
09:39Establishing Mouse Models for Zika Virus-induced Neurological Disorders Using Intracerebral Injection Strategies: Embryonic, Neonatal, and Adult
Published on: April 26, 2018