A specific EMC subunit supports Dengue virus infection by promoting virus membrane fusion essential for cytosolic genome delivery

Bagchi, Parikshit; Speckhart, Kaitlyn; Kennedy, Andrew; Tai, Andrew W.; Tsai, Billy

doi:10.1371/journal.ppat.1010717

Cited by 3 publications

(1 citation statement)

References 26 publications

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“…Intriguingly, the EMC subunit 4 was also shown to promote fusion of the DENV and endosomal membranes to enable the release of the viral RNA into the cytosol. More specifically, EMC4 was shown to promote the transfer of phosphatidylserine, a phospholipid which facilitates DENV-endosomal membrane fusion, from the ER to the endosomes through stabilization of their contact site 65 . This indicates that an ER-localized host factor can also be involved in endosomal membrane fusion thereby regulating an early entry step of DENV infection.…”

Section: The Ermentioning

confidence: 99%

The endoplasmic reticulum (ER): a crucial cellular hub in flavivirus infection and potential target site for antiviral interventions

Verhaegen,

Vermeire

2024

npj Viruses

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Dengue virus (DENV) is the most prevalent arthropod-borne flavivirus and imposes a significant healthcare threat worldwide. At present no FDA-approved specific antiviral treatment is available, and the safety of a vaccine against DENV is still on debate. Following its entry into the host cell, DENV takes advantage of the cellular secretory pathway to produce new infectious particles. The key organelle of the host cell in DENV infections is the endoplasmic reticulum (ER) which supports various stages throughout the entire life cycle of flaviviruses. This review delves into the intricate interplay between flaviviruses and the ER during their life cycle with a focus on the molecular mechanisms underlying viral replication, protein processing and virion assembly. Emphasizing the significance of the ER in the flavivirus life cycle, we highlight potential antiviral targets in ER-related steps during DENV replication and summarize the current antiviral drugs that are in (pre)clinical developmental stage. Insights into the exploitation of the ER by DENV offer promising avenues for the development of targeted antiviral strategies, providing a foundation for future research and therapeutic interventions against flaviviruses.

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Section: The Ermentioning

confidence: 99%

The endoplasmic reticulum (ER): a crucial cellular hub in flavivirus infection and potential target site for antiviral interventions

Verhaegen,

Vermeire

2024

npj Viruses

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How host ER membrane chaperones and morphogenic proteins support virus infection

Woo

Williams

Tsai

2023

Journal of Cell Science

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The multi-functional endoplasmic reticulum (ER) is exploited by viruses to cause infection. Morphologically, this organelle is a highly interconnected membranous network consisting of sheets and tubules whose levels are dynamic, changing in response to cellular conditions. Functionally, the ER is responsible for protein synthesis, folding, secretion and degradation, as well as Ca2+ homeostasis and lipid biosynthesis, with each event catalyzed by defined ER factors. Strikingly, these ER host factors are hijacked by viruses to support different infection steps, including entry, translation, replication, assembly and egress. Although the full repertoire of these ER factors that are hijacked is unknown, recent studies have uncovered several ER membrane machineries that are exploited by viruses – ranging from polyomavirus to flavivirus and coronavirus – to facilitate different steps of their life cycle. These discoveries should provide better understanding of virus infection mechanisms, potentially leading to the development of more effective anti-viral therapies.

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Nifuroxazide Prevents Chikungunya Virus Infection Both In Vitro and In Vivo via Suppressing Viral Replication

Liu,

Xu,

Xia

et al. 2024

Viruses

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Chikungunya virus (CHIKV) is a reemerging arbovirus causing disease on a global scale, and the potential for its epidemics remains high. CHIKV has caused millions of cases and heavy economic burdens around the world, while there are no available approved antiviral therapies to date. In this study, nifuroxazide, an FDA-approved antibiotic for acute diarrhea or colitis, was found to significantly inhibit a variety of arboviruses, although its antiviral activity varied among different target cell types. Nifuroxazide exhibited relatively high inhibitory efficiency in yellow fever virus (YFV) infection of the hepatoma cell line Huh7, tick-borne encephalitis virus (TBEV) and west nile virus (WNV) infection of the vascular endothelial cell line HUVEC, and CHIKV infection of both Huh7 cells and HUVECs, while it barely affected the viral invasion of neurons. Further systematic studies on the action stage of nifuroxazide showed that nifuroxazide mainly inhibited in the viral replication stage. In vivo, nifuroxazide significantly reduced the viral load in muscles and protected mice from CHIKV-induced footpad swelling, an inflammation injury within the arthrosis of infected mice. These results suggest that nifuroxazide has a potential clinical application as an antiviral drug, such as in the treatment of CHIKV infection.

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A specific EMC subunit supports Dengue virus infection by promoting virus membrane fusion essential for cytosolic genome delivery

Cited by 3 publications

References 26 publications

The endoplasmic reticulum (ER): a crucial cellular hub in flavivirus infection and potential target site for antiviral interventions

The endoplasmic reticulum (ER): a crucial cellular hub in flavivirus infection and potential target site for antiviral interventions

How host ER membrane chaperones and morphogenic proteins support virus infection

Nifuroxazide Prevents Chikungunya Virus Infection Both In Vitro and In Vivo via Suppressing Viral Replication

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