Back to Search
Start Over
IP-10 and CXCR3 signaling inhibit Zika virus replication in human prostate cells.
- Source :
-
PloS one [PLoS One] 2020 Dec 30; Vol. 15 (12), pp. e0244587. Date of Electronic Publication: 2020 Dec 30 (Print Publication: 2020). - Publication Year :
- 2020
-
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.<br />Competing Interests: The authors have declared that no competing interests exist.
- Subjects :
- Animals
Cell Line
Cell Proliferation
Cell Survival
Chemokine CXCL10 genetics
Culicidae virology
Gene Expression Regulation
Haplorhini virology
Humans
Immunity, Innate
Male
Prostate cytology
Prostate immunology
Receptors, CXCR3 genetics
Serial Passage
Signal Transduction
Virus Replication
Zika Virus immunology
Zika Virus Infection genetics
Zika Virus Infection virology
Chemokine CXCL10 metabolism
Prostate virology
Receptors, CXCR3 metabolism
Zika Virus physiology
Zika Virus Infection immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 15
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 33378361
- Full Text :
- https://doi.org/10.1371/journal.pone.0244587