LAMR1 Restricts Zika Virus Infection by Attenuating the Envelope Protein Ubiquitination

Overview

Journal Virulence

Specialty Microbiology

Date 2021 Jul 20

PMID 34282707

Citations 10

Authors

Dingwen Hu

Yingchong Wang

Aixin Li

Qin Li

Caifeng Wu

Muhammad Adnan Shereen

Shanyu Huang

Kailang Wu

Ying Zhu

Wenbiao Wang

Jianguo Wu

Affiliations

Soon will be listed here.

Abstract

Zika virus (ZIKV) infection can cause severe neurological disorders, including Guillain-Barre syndrome and meningoencephalitis in adults and microcephaly in fetuses. Here, we reveal that laminin receptor 1 (LAMR1) is a novel host resistance factor against ZIKV infection. Mechanistically, we found that LAMR1 binds to ZIKV envelope (E) protein its intracellular region and attenuates E protein ubiquitination through recruiting the deubiquitinase eukaryotic translation initiation factor 3 subunit 5 (EIF3S5). We further found that the conserved G282 residue of E protein is essential for its interaction with LAMR1. Moreover, a G282A substitution abolished the binding of E protein to LAMR1 and inhibited LAMR1-mediated E protein deubiquitination. Together, our results indicated that LAMR1 represses ZIKV infection through binding to E protein and attenuating its ubiquitination.

Citing Articles

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References

DICK G, KITCHEN S, HADDOW A . Zika virus. I. Isolations and serological specificity. Trans R Soc Trop Med Hyg. 1952; 46(5):509-20. DOI: 10.1016/0035-9203(52)90042-4. View

Lindenbach B, Rice C . Molecular biology of flaviviruses. Adv Virus Res. 2003; 59:23-61. DOI: 10.1016/s0065-3527(03)59002-9. View

Moretti J, Chastagner P, Gastaldello S, Heuss S, Dirac A, Bernards R . The translation initiation factor 3f (eIF3f) exhibits a deubiquitinase activity regulating Notch activation. PLoS Biol. 2010; 8(11):e1000545. PMC: 2990700. DOI: 10.1371/journal.pbio.1000545. View

Hohenester E, Yurchenco P . Laminins in basement membrane assembly. Cell Adh Migr. 2012; 7(1):56-63. PMC: 3544787. DOI: 10.4161/cam.21831. View

Johansson M, Mier-Y-Teran-Romero L, Reefhuis J, Gilboa S, Hills S . Zika and the Risk of Microcephaly. N Engl J Med. 2016; 375(1):1-4. PMC: 4945401. DOI: 10.1056/NEJMp1605367. View

Musso D, Gubler D . Zika Virus. Clin Microbiol Rev. 2016; 29(3):487-524. PMC: 4861986. DOI: 10.1128/CMR.00072-15. View

OFENGAND J, Bakin A . Mapping to nucleotide resolution of pseudouridine residues in large subunit ribosomal RNAs from representative eukaryotes, prokaryotes, archaebacteria, mitochondria and chloroplasts. J Mol Biol. 1997; 266(2):246-68. DOI: 10.1006/jmbi.1996.0737. View

Mesev E, LeDesma R, Ploss A . Decoding type I and III interferon signalling during viral infection. Nat Microbiol. 2019; 4(6):914-924. PMC: 6554024. DOI: 10.1038/s41564-019-0421-x. View

White M, Wollebo H, Beckham J, Tyler K, Khalili K . Zika virus: An emergent neuropathological agent. Ann Neurol. 2016; 80(4):479-89. PMC: 5086418. DOI: 10.1002/ana.24748. View

10.

Fontes C, Dos Santos A, Marchiori E . Magnetic resonance imaging findings in Guillain-Barré syndrome caused by Zika virus infection. Neuroradiology. 2016; 58(8):837-8. DOI: 10.1007/s00234-016-1687-9. View

11.

Khumalo T, Ferreira E, Jovanovic K, Veale R, Weiss S . Knockdown of LRP/LR Induces Apoptosis in Breast and Oesophageal Cancer Cells. PLoS One. 2015; 10(10):e0139584. PMC: 4591328. DOI: 10.1371/journal.pone.0139584. View

12.

Ngueyen T, Kim S, Lee J, Myoung J . Zika Virus Proteins NS2A and NS4A Are Major Antagonists that Reduce IFN-β Promoter Activity Induced by the MDA5/RIG-I Signaling Pathway. J Microbiol Biotechnol. 2019; 29(10):1665-1674. DOI: 10.4014/jmb.1909.09017. View

13.

Kuhn R, Zhang W, Rossmann M, Pletnev S, Corver J, Lenches E . Structure of dengue virus: implications for flavivirus organization, maturation, and fusion. Cell. 2002; 108(5):717-25. PMC: 4152842. DOI: 10.1016/s0092-8674(02)00660-8. View

14.

Hara K, Satoh K, Ide H . Apical ectodermal ridge-dependent expression of the chick 67 kDa laminin binding protein gene (cLbp) in developing limb bud. Zoolog Sci. 1998; 14(6):969-78. DOI: 10.2108/zsj.14.969. View

15.

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

16.

Yang D, Li N, Wei D, Liu B, Guo F, Elbahesh H . The E3 ligase TRIM56 is a host restriction factor of Zika virus and depends on its RNA-binding activity but not miRNA regulation, for antiviral function. PLoS Negl Trop Dis. 2019; 13(6):e0007537. PMC: 6623546. DOI: 10.1371/journal.pntd.0007537. View

17.

Govero J, Esakky P, Scheaffer S, Fernandez E, Drury A, Platt D . Zika virus infection damages the testes in mice. Nature. 2016; 540(7633):438-442. PMC: 5432198. DOI: 10.1038/nature20556. View

18.

Savidis G, Perreira J, Portmann J, Meraner P, Guo Z, Green S . The IFITMs Inhibit Zika Virus Replication. Cell Rep. 2016; 15(11):2323-30. DOI: 10.1016/j.celrep.2016.05.074. View

19.

Duffy M, Chen T, Hancock W, Powers A, Kool J, Lanciotti R . Zika virus outbreak on Yap Island, Federated States of Micronesia. N Engl J Med. 2009; 360(24):2536-43. DOI: 10.1056/NEJMoa0805715. View

20.

Ma W, Li S, Ma S, Jia L, Zhang F, Zhang Y . Zika Virus Causes Testis Damage and Leads to Male Infertility in Mice. Cell. 2016; 167(6):1511-1524.e10. DOI: 10.1016/j.cell.2016.11.016. View