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Updated: Jul 30, 2026
Zika Virus Infectious Cell Culture System and the In Vitro Prophylactic Effect of Interferons
Published on: August 23, 2016
IP-10 and CXCR3 signaling inhibit Zika virus replication in human prostate cells
Jennifer L Spencer Clinton1, Linda L Tran2,3, Megan B Vogt2
1Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, United States of America.
Abstract:
Our previous studies have shown that Zika virus (ZIKV) replicates in human prostate cells, suggesting that the prostate may serve as a long-term reservoir for virus transmission. Here, we demonstrated that the innate immune responses generated to three distinct ZIKV strains (all isolated from human serum) were significantly different and dependent on their passage history (in mosquito, monkey, or human cells). In addition, some of these phenotypic differences were reduced by a single additional cell culture passage, suggesting that viruses that have been passaged more than 3 times from the patient sample will no longer reflect natural phenotypes. Two of the ZIKV strains analyzed induced high levels of the IP-10 chemokine and IFNγ in human prostate epithelial and stromal mesenchymal stem cells. To further understand the importance of these innate responses on ZIKV replication, we measured the effects of IP-10 and its downstream receptor, CXCR3, on RNA and virus production in prostate cells. Treatment with IP-10, CXCR3 agonist, or CXCR3 antagonist significantly altered ZIKV viral gene expression, depending on their passage in cells of relevant hosts (mosquito or human). We detected differences in gene expression of two primary CXCR3 isoforms (CXCR3-A and CXCR3-B) on the two cell types, possibly explaining differences in viral output. Lastly, we examined the effects of IP-10, agonist, or antagonist on cell death and proliferation under physiologically relevant infection rates, and detected no significant differences. Although we did not measure protein expression directly, our results indicate that CXCR3 signaling may be a target for therapeutics, to ultimately stop sexual transmission of this virus.
Insights
Zika virus (ZIKV) exhibits varied immune responses in prostate cells based on strain and passage history. Targeting the IP-10/CXCR3 pathway shows potential for preventing sexual transmission of ZIKV.
Area of Science:
- Virology
- Immunology
- Cell Biology
Background:
- Zika virus (ZIKV) replicates in human prostate cells, indicating the prostate as a potential viral reservoir.
- Innate immune responses to ZIKV strains vary significantly based on their passage history in different host cells.
Purpose of the Study:
- To investigate the differential innate immune responses to distinct ZIKV strains in human prostate cells.
- To determine the role of IP-10 and its receptor CXCR3 in ZIKV replication and gene expression within prostate cells.
- To explore the potential of targeting the IP-10/CXCR3 pathway for therapeutic intervention against ZIKV sexual transmission.
Main Methods:
- Analysis of innate immune responses (IP-10, IFNγ) to three ZIKV strains with varying passage histories in human prostate epithelial and stromal mesenchymal stem cells.
- Assessment of ZIKV RNA and virus production following treatment with IP-10, CXCR3 agonist, or CXCR3 antagonist.
- Evaluation of CXCR3 isoform (CXCR3-A, CXCR3-B) gene expression in response to ZIKV infection.
- Examination of the effects of IP-10, agonist, or antagonist on cell death and proliferation.
Main Results:
- Significant differences in innate immune responses were observed among ZIKV strains, influenced by passage history, with some differences diminishing after additional cell culture passages.
- Two ZIKV strains induced high levels of IP-10 and IFNγ in prostate cells.
- IP-10 and CXCR3 signaling modulation significantly altered ZIKV gene expression, with effects dependent on viral passage history.
- Differential expression of CXCR3-A and CXCR3-B isoforms was detected in prostate cell types, potentially explaining variations in viral output.
- No significant impact of IP-10 or CXCR3 modulation on cell death or proliferation was observed at relevant infection rates.
Conclusions:
- ZIKV strain phenotype and replication dynamics are heavily influenced by passage history, underscoring the importance of using viruses with minimal passage for research.
- The IP-10/CXCR3 signaling axis plays a crucial role in modulating ZIKV replication and gene expression in prostate cells.
- CXCR3 signaling represents a promising therapeutic target to inhibit ZIKV replication and prevent sexual transmission.
