ZIKV Infection Differentially Affects the Transcriptional Profiles in HTR8 and U251 Cells

Overview

Journal Virus Res

Specialty Microbiology

Date 2023 Jun 30

PMID 37390859

Authors

Qiqi Chen

Nina Li

Shike Zeng

Shu Wu

Xin Luo

Shengze Zhang

Lin Zhu

Jiani Wu

Ting Xie

Shaohui Bai

Hao Zhang

Zhiyuan Jiang

Shaoli Lin

Nan Wu

Ying Jiang

Shisong Fang

Xin Wang

Yuelong Shu

Huanle Luo

Affiliations

Soon will be listed here.

Abstract

The mechanism by which Zika virus (ZIKV) causes severe birth defects in pregnant women remains unclear. Cell tropisms in placenta and brain play a crucial role in ZIKV pathogenesis, leading to congenital Zika syndrome (CZS). To identify the host factors involved in ZIKV infection, we compared the transcriptional profiles of ZIKV-infected human first-trimester placental trophoblast cells HTR8/SVneo and a human glioblastoma astrocytoma cell line U251. Our results demonstrated that ZIKV exhibited lower rates of mRNA replication and protein expression in HTR8 than in U251 cells, while showing a higher release of infectious viral particles. However, a greater number of differentially expressed genes (DEGs) were found in ZIKV-infected U251 cells than in ZIKV-infected HTR8 cells. Several of these DEGs were enriched in distinct biological processes related to the characteristics of each cell type that may contribute to foetal damage. Both cell types exhibited activation of common interferons, inflammatory cytokines, and chemokine production upon ZIKV infection. Moreover, the neutralization of tumour necrosis factor-alpha (TNF-α) promoted ZIKV infection in both trophoblasts and glioblastoma astrocytoma cells. Overall, we identified multiple DEGs associated with ZIKV pathogenesis.

References

Kung P, Chou T, Lindman M, Chang N, Estevez I, Buckley B . Zika virus-induced TNF-α signaling dysregulates expression of neurologic genes associated with psychiatric disorders. J Neuroinflammation. 2022; 19(1):100. PMC: 9036774. DOI: 10.1186/s12974-022-02460-8. View

Lum F, Low D, Fan Y, Tan J, Lee B, Chan J . Zika Virus Infects Human Fetal Brain Microglia and Induces Inflammation. Clin Infect Dis. 2017; 64(7):914-920. DOI: 10.1093/cid/ciw878. View

Hughes B, Addanki K, Sriskanda A, McLean E, Bagasra O . Infectivity of Immature Neurons to Zika Virus: A Link to Congenital Zika Syndrome. EBioMedicine. 2016; 10:65-70. PMC: 5006602. DOI: 10.1016/j.ebiom.2016.06.026. View

Cofre F . [Zika virus intrauterine infection causes fetal brain abnormality and microcephaly: tip of the iceberg?]. Rev Chilena Infectol. 2016; 33(1):96. DOI: 10.4067/S0716-10182016000100018. View

Mladinich M, Conde J, Schutt W, Sohn S, Mackow E . Blockade of Autocrine CCL5 Responses Inhibits Zika Virus Persistence and Spread in Human Brain Microvascular Endothelial Cells. mBio. 2021; 12(4):e0196221. PMC: 8406327. DOI: 10.1128/mBio.01962-21. View

Caires-Junior L, Goulart E, Melo U, Araujo B, Alvizi L, Soares-Schanoski A . Discordant congenital Zika syndrome twins show differential in vitro viral susceptibility of neural progenitor cells. Nat Commun. 2018; 9(1):475. PMC: 5797251. DOI: 10.1038/s41467-017-02790-9. View

Tabata T, Petitt M, Puerta-Guardo H, Michlmayr D, Wang C, Fang-Hoover J . Zika Virus Targets Different Primary Human Placental Cells, Suggesting Two Routes for Vertical Transmission. Cell Host Microbe. 2016; 20(2):155-66. PMC: 5257282. DOI: 10.1016/j.chom.2016.07.002. View

de Sousa J, Azevedo R, Martins Filho A, Araujo M, Moutinho E, Baldez Vasconcelos B . Correlation between Apoptosis and in Situ Immune Response in Fatal Cases of Microcephaly Caused by Zika Virus. Am J Pathol. 2018; 188(11):2644-2652. DOI: 10.1016/j.ajpath.2018.07.009. View

Kumar A, Jovel J, Lopez-Orozco J, Limonta D, Airo A, Hou S . Human Sertoli cells support high levels of Zika virus replication and persistence. Sci Rep. 2018; 8(1):5477. PMC: 5883016. DOI: 10.1038/s41598-018-23899-x. View

10.

Wikan N, Smith D . Zika virus: history of a newly emerging arbovirus. Lancet Infect Dis. 2016; 16(7):e119-e126. DOI: 10.1016/S1473-3099(16)30010-X. View

11.

Alpuche-Lazcano S, Saliba J, Costa V, Campolina-Silva G, Marim F, Ribeiro L . Profound downregulation of neural transcription factor Npas4 and Nr4a family in fetal mice neurons infected with Zika virus. PLoS Negl Trop Dis. 2021; 15(5):e0009425. PMC: 8191876. DOI: 10.1371/journal.pntd.0009425. View

12.

Hirsch A, Roberts V, Grigsby P, Haese N, Schabel M, Wang X . Zika virus infection in pregnant rhesus macaques causes placental dysfunction and immunopathology. Nat Commun. 2018; 9(1):263. PMC: 5772047. DOI: 10.1038/s41467-017-02499-9. View

13.

Strange D, Jiyarom B, Sadri-Ardekani H, Cazares L, Kenny T, Ward M . Paracrine IFN Response Limits ZIKV Infection in Human Sertoli Cells. Front Microbiol. 2021; 12:667146. PMC: 8165286. DOI: 10.3389/fmicb.2021.667146. View

14.

Mlakar J, Korva M, Tul N, Popovic M, Poljsak-Prijatelj M, Mraz J . Zika Virus Associated with Microcephaly. N Engl J Med. 2016; 374(10):951-8. DOI: 10.1056/NEJMoa1600651. View

15.

Antoniou E, Orovou E, Sarella A, Iliadou M, Rigas N, Palaska E . Zika Virus and the Risk of Developing Microcephaly in Infants: A Systematic Review. Int J Environ Res Public Health. 2020; 17(11). PMC: 7312578. DOI: 10.3390/ijerph17113806. View

16.

Daniels B, Kofman S, Smith J, Norris G, Snyder A, Kolb J . The Nucleotide Sensor ZBP1 and Kinase RIPK3 Induce the Enzyme IRG1 to Promote an Antiviral Metabolic State in Neurons. Immunity. 2019; 50(1):64-76.e4. PMC: 6342485. DOI: 10.1016/j.immuni.2018.11.017. View

17.

Yellowhair T, Newville J, Noor S, Maxwell J, Milligan E, Robinson S . CXCR2 Blockade Mitigates Neural Cell Injury Following Preclinical Chorioamnionitis. Front Physiol. 2019; 10:324. PMC: 6454349. DOI: 10.3389/fphys.2019.00324. View

18.

Xia H, Luo H, Shan C, Muruato A, Nunes B, Medeiros D . An evolutionary NS1 mutation enhances Zika virus evasion of host interferon induction. Nat Commun. 2018; 9(1):414. PMC: 5788864. DOI: 10.1038/s41467-017-02816-2. View

19.

Chang Y, Jiang Y, Li C, Wang Q, Zhang F, Qin C . Different Gene Networks Are Disturbed by Zika Virus Infection in A Mouse Microcephaly Model. Genomics Proteomics Bioinformatics. 2021; 18(6):737-748. PMC: 8377042. DOI: 10.1016/j.gpb.2019.06.004. View

20.

Bindea G, Mlecnik B, Hackl H, Charoentong P, Tosolini M, Kirilovsky A . ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks. Bioinformatics. 2009; 25(8):1091-3. PMC: 2666812. DOI: 10.1093/bioinformatics/btp101. View