Lipid balance remodelling by human positive-strand RNA viruses and the contribution of lysosomes

Lai, Michele; Carli, Alessandro De; Filipponi, Carolina; Iacono, Elena; Rocca, Veronica La; Lottini, Giulia; Piazza, Carmen Rita; Quaranta, Paola; Sidoti, Maria; Pistello, Mauro; Freer, Giulia

doi:10.1016/j.antiviral.2022.105398

Cited by 11 publications

(9 citation statements)

References 172 publications

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“…The interplay between the LDs and the viral infectious cycles has recently become a well-explored field, with the LDs serving not only as a scaffold for replication and assembly, but also as a source of energy or membrane lipids [ 64 , 65 , 66 , 67 , 68 ]. Having observed a significant increase in the number of LDs in IBDV-infected cells and discarded their role as assembly platforms, we sought to analyze their potentially beneficial role in the viral cycle.…”

Section: Resultsmentioning

confidence: 99%

Infectious Bursal Disease Virus Assembly Causes Endoplasmic Reticulum Stress and Lipid Droplet Accumulation

Frontini-López

Rivera

Pocognoni

et al. 2023

Viruses

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Gumboro illness is caused by the highly contagious immunosuppressive infectious bursal disease virus (IBDV), which affects the poultry industry globally. We have previously shown that IBDV hijacks the endocytic pathway to construct viral replication complexes on endosomes linked to the Golgi complex (GC). Then, analyzing crucial proteins involved in the secretory pathway, we showed the essential requirement of Rab1b, the Rab1b downstream effector Golgi-specific BFA resistance factor 1 (GBF1), and its substrate, the small GTPase ADP-ribosylation factor 1 (ARF1), for IBDV replication. In the current work, we focused on elucidating the IBDV assembly sites. We show that viral assembly occurs within single-membrane compartments closely associated with endoplasmic reticulum (ER) membranes, though we failed to elucidate the exact nature of the virus-wrapping membranes. Additionally, we show that IBDV infection promotes the stress of the ER, characterized by an accumulation of the chaperone binding protein (BiP) and lipid droplets (LDs) in the host cells. Overall, our results represent further original data showing the interplay between IBDV and the secretory pathway, making a substantial contribution to the field of birnaviruses–host cell interactions.

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Section: Resultsmentioning

confidence: 99%

Infectious Bursal Disease Virus Assembly Causes Endoplasmic Reticulum Stress and Lipid Droplet Accumulation

Frontini-López

Rivera

Pocognoni

et al. 2023

Viruses

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“…To provide large amounts of membrane required for RO formation, enteroviruses developed numerous ways to manipulate host cell pathways for biogenesis and functionality of the membranous structures in infected cells [48,49]. Some viral proteins must be therefore associated with membranes to properly execute their function and realize the viral life cycle.…”

Section: Discussionmentioning

confidence: 99%

Leucoverdazyls as novel potent inhibitors of enterovirus replication

Volobueva,

Fedorchenko,

Lipunova

et al. 2024

Preprint

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Enteroviruses (EV) are important pathogens causing human disease with various clinical manifestations. To date, treatment of enteroviral infections is mainly supportive since no vaccination or antiviral drugs are approved for their prevention or treatment. Here, we describe the antiviral properties and mechanisms of action of leucoverdazyls - novel heterocyclic compounds with antioxidant potential. The lead compound, 1a, demonstrated low cytotoxicity along with high antioxidant and virus-inhibiting activity. A viral strain resistant to 1a was selected, and the development of resistance was shown to be accompanied by mutation of virus-specific non-structural protein 2C. This resistant virus had lower fitness when grown in cell culture. Taken together, our results demonstrate high antiviral potential of leucoverdazyls as novel inhibitors of enterovirus replication and support previous evidence of an important role of 2C proteins in EV replication.

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“…(2) LD Remodeling: Once associated with LDs, viral replication complexes undergo rearrangement and remodeling [71]. This process is essential for creating an environment conducive to efficient viral RNA synthesis and replication.…”

Section: Ld and Viruses In Generalmentioning

confidence: 99%

Lipid Droplets: Formation, Degradation, and Their Role in Cellular Responses to Flavivirus Infections

Hsia,

Liu,

Haynes

et al. 2024

Microorganisms

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Lipid droplets (LDs) are cellular organelles derived from the endoplasmic reticulum (ER), serving as lipid storage sites crucial for maintaining cellular lipid homeostasis. Recent attention has been drawn to their roles in viral replication and their interactions with viruses. However, the precise biological functions of LDs in viral replication and pathogenesis remain incompletely understood. To elucidate the interaction between LDs and viruses, it is imperative to comprehend the biogenesis of LDs and their dynamic interactions with other organelles. In this review, we explore the intricate pathways involved in LD biogenies within the cytoplasm, encompassing the uptake of fatty acid from nutrients facilitated by CD36-mediated membranous protein (FABP/FATP)-FA complexes, and FA synthesis via glycolysis in the cytoplasm and the TCL cycle in mitochondria. While LD biogenesis primarily occurs in the ER, matured LDs are intricately linked to multiple organelles. Viral infections can lead to diverse consequences in terms of LD status within cells post-infection, potentially involving the breakdown of LDs through the activation of lipophagy. However, the exact mechanisms underlying LD destruction or accumulation by viruses remain elusive. The significance of LDs in viral replication renders them effective targets for developing broad-spectrum antivirals. Moreover, considering that reducing neutral lipids in LDs is a strategy for anti-obesity treatment, LD depletion may not pose harm to cells. This presents LDs as promising antiviral targets for developing therapeutics that are minimally or non-toxic to the host.

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Lipid balance remodelling by human positive-strand RNA viruses and the contribution of lysosomes

Cited by 11 publications

References 172 publications

Infectious Bursal Disease Virus Assembly Causes Endoplasmic Reticulum Stress and Lipid Droplet Accumulation

Infectious Bursal Disease Virus Assembly Causes Endoplasmic Reticulum Stress and Lipid Droplet Accumulation

Leucoverdazyls as novel potent inhibitors of enterovirus replication

Lipid Droplets: Formation, Degradation, and Their Role in Cellular Responses to Flavivirus Infections

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