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Updated: Oct 27, 2025
Isolation and Quantification of Zika Virus from Multiple Organs in a Mouse
Published on: August 15, 2019
LAMR1 restricts Zika virus infection by attenuating the envelope protein ubiquitination
Dingwen Hu1, Yingchong Wang1, Aixin Li1
1State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan China.
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 via 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.
Insights
Laminin receptor 1 (LAMR1) acts as a host defense against Zika virus (ZIKV) by binding to its envelope protein. This interaction reduces viral replication by preventing essential protein ubiquitination.
Area of Science:
- Virology
- Molecular Biology
- Immunology
Background:
- Zika virus (ZIKV) poses significant public health risks, causing severe neurological conditions like microcephaly and Guillain-Barre syndrome.
- Understanding host-pathogen interactions is crucial for developing effective antiviral strategies against ZIKV.
Purpose of the Study:
- To identify novel host factors that confer resistance against Zika virus infection.
- To elucidate the molecular mechanism by which laminin receptor 1 (LAMR1) inhibits ZIKV replication.
Main Methods:
- Investigated the interaction between LAMR1 and ZIKV envelope (E) protein using molecular binding assays.
- Assessed the role of LAMR1 in modulating E protein ubiquitination by employing co-immunoprecipitation and Western blotting.
- Utilized site-directed mutagenesis to identify key residues involved in the LAMR1-E protein interaction.
Main Results:
- Identified laminin receptor 1 (LAMR1) as a novel host resistance factor against ZIKV.
- Demonstrated that LAMR1 binds to the ZIKV envelope (E) protein via its intracellular region, recruiting eukaryotic translation initiation factor 3 subunit 5 (EIF3S5) to attenuate E protein ubiquitination.
- Showed that the conserved G282 residue in the ZIKV E protein is critical for LAMR1 binding and subsequent deubiquitination.
Conclusions:
- LAMR1 effectively represses ZIKV infection by directly interacting with the viral E protein.
- The mechanism involves LAMR1-mediated deubiquitination of the E protein, highlighting a new antiviral pathway.
- Targeting the LAMR1-E protein interaction could represent a potential therapeutic strategy against ZIKV.
