Pathogenic RNA Viruses: Mechanisms of Viral Replication, Viral–Host Interactions and Antiviral Development

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Microbiology in Human Health and Disease".

Deadline for manuscript submissions: 30 June 2024 | Viewed by 895

Special Issue Editor


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Guest Editor
Howard Hughes Medical Institute, University of Maryland, Baltimore County, Baltimore, MD, USA
Interests: RNA virus; retrovirus; retrotransposon; protein-RNA interactions; RNA structure and function; non-coding RNA; structural biology; NMR

Special Issue Information

Dear Colleagues,

Many health-threatening human pathogens are RNA viruses, some of which even have pandemic potential, such as coronaviruses (SARS-CoV2), influenza viruses, flaviviruses (Zika virus, Dengue virus, etc.), Ebola virus and hepatitis viruses. Plant and animal RNA viruses can also cause severe economic burdens. Understanding the detailed molecular mechanisms behind RNA virus replication and the virus–host interactions is crucial for developing more effective antiviral strategies to prevent the devastating consequences of highly pathogenic RNA virus infections. On the other hand, RNA viruses are greatly simplified macromolecular systems, which is ideal for the studies of protein–RNA interactions and RNA structure–function relationship. In addition, RNA-virus-derived biologics could also have great potential in biotechnology and therapeutic development. This Special Issue of Biomedicines focuses on recent advances in all aspects of RNA viruses and RNA virus infections. Authors are invited to submit their original research/review articles to Biomedicines on topics including, but not limited to, the following:

  • Molecular mechanisms of viral replication;
  • Viral particle assembly and viral RNA packaging;
  • Structural and functional studies of non-coding RNAs in the viral RNA genome;
  • Interplay between host cell and RNA virus, such as host antiviral responses and viral immune evasion;
  • Vaccine and antiviral therapeutic developments;
  • In vitro assembly of virus-like particles (VLP) and their applications.

Dr. Pengfei Ding
Guest Editor

Manuscript Submission Information

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Keywords

  • RNA virus
  • protein–RNA interactions
  • RNA structure and function
  • virus–host cell interactions
  • virus assembly and replication
  • viral vectors
  • therapeutic development

Published Papers (1 paper)

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Research

15 pages, 28311 KiB  
Article
Co-Expression of Niemann-Pick Type C1-Like1 (NPC1L1) with ACE2 Receptor Synergistically Enhances SARS-CoV-2 Entry and Fusion
by James Elste, Nicole Cast, Shalini Udawatte, Kabita Adhikari, Shannon Harger Payen, Subhash C. Verma, Deepak Shukla, Michelle Swanson-Mungerson and Vaibhav Tiwari
Biomedicines 2024, 12(4), 821; https://doi.org/10.3390/biomedicines12040821 - 8 Apr 2024
Viewed by 662
Abstract
The entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into human embryonic kidney (HEK293T) cells has been shown to be a cholesterol-rich, lipid raft-dependent process. In this study, we investigated if the presence of a cholesterol uptake receptor Niemann-pick type c1-like1 (NPC1L1) [...] Read more.
The entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into human embryonic kidney (HEK293T) cells has been shown to be a cholesterol-rich, lipid raft-dependent process. In this study, we investigated if the presence of a cholesterol uptake receptor Niemann-pick type c1-like1 (NPC1L1) impacts SARS-CoV-2 cell entry. Initially, we utilized reporter-based pseudovirus cell entry assays and a spike (S) glycoprotein-mediated cell-to-cell fusion assay. Using Chinese hamster ovary (CHO-K1) cells, which lack endogenous receptors for SARS-CoV-2 entry, our data showed that the co-expression of NPC1L1 together with the ACE2 receptor synergistically increased SARS-CoV-2 pseudovirus entry even more than the cells expressing ACE-2 receptor alone. Similar results were also found with the HEK293T cells endogenously expressing the ACE2 receptor. Co-cultures of effector cells expressing S glycoprotein together with target cells co-expressing ACE-2 receptor with NPC1L1 significantly promoted quantitative cell-to-cell fusion, including syncytia formation. Finally, we substantiated that an elevated expression of NPC1L1 enhanced entry, whereas the depletion of NPC1L1 resulted in a diminished SARS-CoV-2 entry in HEK293T-ACE2 cells using authentic SARS-CoV-2 virus in contrast to their respective control cells. Collectively, these findings underscore the pivotal role of NPC1L1 in facilitating the cellular entry of SARS-CoV-2. Importance: Niemann-Pick type C1-like1 (NPC1L1) is an endosomal membrane protein that regulates intracellular cholesterol trafficking. This protein has been demonstrated to play a crucial role in the life cycle of several clinically important viruses. Although SARS-CoV-2 exploits cholesterol-rich lipid rafts as part of its viral entry process, the role of NPC1L1 in SARS-CoV-2 entry remains unclear. Our research represents the first-ever demonstration of NPC1L1’s involvement in facilitating SARS-CoV-2 entry. The observed role of NPC1L1 in human kidney cells is not only highly intriguing but also quite relevant. This relevance stems from the fact that NPC1L1 exhibits high expression levels in several organs, including the kidneys, and the fact that kidney damages are reported during severe cases of SARS-CoV-2. These findings may help us understand the new functions and mechanisms of NPC1L1 and could contribute to the identification of new antiviral targets. Full article
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