Role of heparan sulfate in the Zika virus entry, replication, and cell death

Gao, Huixin; Lin, Yuxia; He, Jun; Zhou, Suna; Liang, Mujiao; Huang, Chenghui; Li, Xiaobo; Liu, Chao; Zhang, Ping

doi:10.1016/j.virol.2019.01.019

Cited by 43 publications

(28 citation statements)

References 36 publications

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“…Generation of HCAR2-Knockout Cell Clones CRISPR/Cas9 system was utilized to generate HCAR2-knockout cell clones as previously described (Ran et al, 2013;Gao et al, 2019). sgRNAs were designed and cloned into the vector, lentiCRIPSR v2 (Addgene #52961).…”

Section: Western Blottingmentioning

confidence: 99%

“…Van der Hoek et al reported that Viperin, one of the interferon stimulated genes, functions as a restriction factor in control of ZIKV infection (Van der Hoek et al, 2017). Furthermore, through screens of orthologous functional genomic using RNAi and CRISPR/Cas9 approaches, multiple host factors have been identified to be involved in the life cycle of ZIKV, including entry factor [AXL receptor tyrosine kinase (AXL)], endocytosis-related factors [RAB5C, member RAS oncogene family (RAB5C) and RAB guanine nucleotide exchange factor (RABGEF)], heparin sulfation-related factors [N-Deacetylase and N-Sulfotransferase 1 (NDST1), exostosin glycosyltransferase 1 (EXT1), and heparan sulfate], and the endoplasmic reticulum membrane complex (EMC) (Savidis et al, 2016b;Meertens et al, 2017;Gao et al, 2019). Nonetheless, many other ZIKV-related host factors remain to be determined.…”

Section: Introductionmentioning

confidence: 99%

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Hydroxycarboxylic Acid Receptor 2 Is a Zika Virus Restriction Factor That Can Be Induced by Zika Virus Infection Through the IRE1-XBP1 Pathway

Luo

Zhou

et al. 2020

Front. Cell. Infect. Microbiol.

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Zika virus (ZIKV) is an emerging arthropod-borne virus and belongs to the Flaviviridae family. The infection of ZIKV has become the global health crisis because of its rapid spread and association with severe neurological disorders, including congenital microcephaly and Guillain-Barre Syndrome. To identify host factors contributing to ZIKV pathogenesis, transcriptomic landscape in ZIKV-infected cells was examined with mRNA microarray analysis and we observed that the expression of hydroxycarboxylic acid receptor 2 (HCAR2) could be significantly induced by ZIKV infection. By utilizing two IRE1 inhibitors and XBP1-specific shRNAs, we revealed that the up-regulation of HCAR2 expression induced by ZIKV was dependent on the IRE1-XBP1 pathway. Through the CRISPR/Cas9 system, we generated HCAR2-deficient cell clones in two cell types (human lung carcinoma epithelial A549 cell and human hepatoma Huh7.5 cell). We found that the depletion of HCAR2 significantly increased the replication level of ZIKV, including RNA levels, protein expression levels, and viral titers. In addition, our data demonstrated that the antiviral effect of HCAR2 was not involved in viral entry process and was not dependent on its antilipolytic effect on nicotinic acid/HCAR2-mediated signaling pathway. Taken together, our results indicated that HCAR2 could function as a restriction factor in control of ZIKV replication, potentially providing a novel molecular target for anti-ZIKV therapeutics.

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Section: Western Blottingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Hydroxycarboxylic Acid Receptor 2 Is a Zika Virus Restriction Factor That Can Be Induced by Zika Virus Infection Through the IRE1-XBP1 Pathway

Luo

Zhou

et al. 2020

Front. Cell. Infect. Microbiol.

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“…The PCR primer sequences were listed in Table 2 . PCR product was inserted into pSG5 vector or a lentiviral vector CSII–EF–MCS–IRES2–Venus and sequenced as described previously ( Gao et al, 2019 ). The resulting plasmids were designated as pSG5–ANKS4B–FLAG and pCSII–EF–MCS–IRES2–Venus–ANKS4B.…”

Section: Methodsmentioning

confidence: 99%

ANKS4B Restricts Replication of Zika Virus by Downregulating the Autophagy

et al. 2020

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Infection of Zika virus (ZIKV) has become a severe threaten to global health while no specific drug is available. In this study, we explored the relationship between ZIKV and a cellular protein, ankyrin repeat and sterile motif domain containing 4b (ANKS4B). Our data revealed that the expression of ANKS4B in cultured cells and in neonatal mice was downregulated by ZIKV infection. The reduction of ANKS4B upon ZIKV infection was caused by decrease of two hepatocyte nuclear factors HNF1α and HNF4α . Through CRISPR/Cas9 gene editing system, we generated two ANKS4B knockout (KO) cell clones in A549 and Huh7 cells respectively. In the ANKS4B-KO cells, the viral replication levels including viral RNA, protein, and titer were significantly enhanced, which was reversed by trans -complementation of ANKS4B. ANKS4B did not affect the viral entry step, but impaired the autophagy induced by ZIKV infection. Furthermore, our data showed that inhibition of autophagy led to similar replication levels of ZIKV in ANKS4B-sufficient and ANKS4B-deficient cells, suggesting the antiviral effect of ANKS4B relied on its modulation on the autophagy. Therefore, our work identified ANKS4B as a new restriction factor of ZIKV.

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“…[ 25 ]; [ 26 ]; [ 27 ]; [ 28 ]; [ 29 ]; [ 30 ]; [ 31 ]; [ 32 ]; [ 33 ]; [ 34 ]; [ 35 ]; [ 36 ]; [ 37 ]; [ 38 ]; [ 39 ]; [ 40 ]; [ 41 ]; [ 42 ]; [ 50 ]; [ 51 ]; [ 81 ]; [ 82 ]; [ 83 ].…”

Section: Uncited Referencesunclassified