The role of lipids in the pathophysiology of coronavirus infections

Zandi, Milad; Hosseini, Parastoo; Soltani, Saber; Rasooli, Azadeh; Moghadami, Mona; Nasimzadeh, Sepideh; Behnezhad, Farzane

doi:10.24171/j.phrp.2021.0153

Cited by 3 publications

(3 citation statements)

References 68 publications

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“…Although some mechanisms have been proposed to explain the role of zinc during virus infection, like the inhibition of viral protein cleavage and processing as well as inhibition of the viral polymerase activity, the experimental data supporting these mechanistic models are lacking ( 54 , 55 , 57 ). Interestingly, the importance of lipids for many of these zinc-sensitive viruses including coronaviruses ( 26 , 89 ), picornaviruses ( 43 , 90 ), and hepatitis E virus ( 91 ), has been reported. Our collective data support a novel hypothetical mechanistic model wherein zinc reduces virus infection via the depletion of lipids and may have broad implications for zinc-sensitive viruses ( Fig.…”

Section: Discussionmentioning

confidence: 99%

Orsay Virus Infection of Caenorhabditis elegans Is Modulated by Zinc and Dependent on Lipids

Casorla-Perez

Guennoun

Cubillas

et al. 2022

J Virol

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Section: Discussionmentioning

confidence: 99%

Orsay Virus Infection of Caenorhabditis elegans Is Modulated by Zinc and Dependent on Lipids

Casorla-Perez

Guennoun

Cubillas

et al. 2022

J Virol

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“…Cellular lipids can participate in several processes of viral proliferation, such as attachment, viral genome replication, and viral budding ( 21 ). SREBF1 is a primary regulator of cellular lipid synthesis and lipid homeostasis ( 22 ).…”

Section: Resultsmentioning

confidence: 99%

PEDV inhibits HNRNPA3 expression by miR-218-5p to enhance cellular lipid accumulation and promote viral replication

Shi,

Zhang,

Yang

et al. 2024

mBio

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Porcine epidemic diarrhea virus (PEDV) requires complete dependence on the metabolic system of the host cell to complete its life cycle. There is a strong link between efficient viral replication and cellular lipid synthesis. However, the mechanism by which PEDV interacts with host cells to hijack cellular lipid metabolism to promote its replication remains unclear. In this study, PEDV infection significantly enhanced the expression of lipid synthesis-related genes and increased cellular lipid accumulation. Furthermore, using liquid chromatography-tandem mass spectrometry, we identified heterogeneous nuclear ribonucleoprotein A3 (HNRNPA3) as the interacting molecule of PEDV NSP9. We demonstrated that the expression of HNRNPA3 was downregulated by PEDV-induced miR-218-5p through targeting its 3′ untranslated region. Interestingly, knocking down HNRNPA3 facilitated the PEDV replication by promoting cellular lipid synthesis. We next found that the knockdown of HNRNPA3 potentiated the transcriptional activity of sterol regulatory element-binding transcription factor 1 (SREBF1) through zinc finger protein 135 (ZNF135) as well as PI3K/AKT and JNK signaling pathways. In summary, we propose a model in which PEDV downregulates HNRNPA3 expression to promote the expression and activation of SREBF1 and increase cellular lipid accumulation, providing a novel mechanism by which PEDV interacts with the host to utilize cellular lipid metabolism to promote its replication. IMPORTANCE As the major components and structural basis of the viral replication complexes of positive-stranded RNA viruses, lipids play an essential role in viral replication. However, how PEDV manipulates host cell lipid metabolism to promote viral replication by interacting with cell proteins remains poorly understood. Here, we found that SREBF1 promotes cellular lipid synthesis, which is essential for PEDV replication. Moreover, HNRNPA3 negatively regulates SREBF1 activation and specifically reduces lipid accumulation, ultimately inhibiting PEDV dsRNA synthesis. Our study provides new insight into the mechanisms by which PEDV hijacks cell lipid metabolism to benefit viral replication, which can offer a potential target for therapeutics against PEDV infection.

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“…The Golgi complex is a cellular organelle that acts like a post office, wrapping molecules in a membrane and shipping them to other locations within the cell. Coronaviruses form a lipid envelope from the membranes of the Golgi complex, and the newly formed virus particles enter Golgi vesicles, are transported to the cell surface, and are expelled from the cell [198][199][200][201]. Coronaviruses can also exit cells through lysosomes.…”

Section: Intracellular Changes With Virus Infectionsmentioning

confidence: 99%

Understanding the Molecular Actions of Spike Glycoprotein in SARS-CoV-2 and Issues of a Novel Therapeutic Strategy for the COVID-19 Vaccine

Matsuzaka,

Yashiro

2024

BioMedInformatics

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In vaccine development, many use the spike protein (S protein), which has multiple “spike-like” structures protruding from the spherical structure of the coronavirus, as an antigen. However, there are concerns about its effectiveness and toxicity. When S protein is used in a vaccine, its ability to attack viruses may be weak, and its effectiveness in eliciting immunity will only last for a short period of time. Moreover, it may cause “antibody-dependent immune enhancement”, which can enhance infections. In addition, the three-dimensional (3D) structure of epitopes is essential for functional analysis and structure-based vaccine design. Additionally, during viral infection, large amounts of extracellular vesicles (EVs) are secreted from infected cells, which function as a communication network between cells and coordinate the response to infection. Under conditions where SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) molecular vaccination produces overwhelming SARS-CoV-2 spike glycoprotein, a significant proportion of the overproduced intracellular spike glycoprotein is transported via EVs. Therefore, it will be important to understand the infection mechanisms of SARA-CoV-2 via EV-dependent and EV-independent uptake into cells and to model the infection processes based on 3D structural features at interaction sites.

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The role of lipids in the pathophysiology of coronavirus infections

Cited by 3 publications

References 68 publications

Orsay Virus Infection of Caenorhabditis elegans Is Modulated by Zinc and Dependent on Lipids

Orsay Virus Infection of Caenorhabditis elegans Is Modulated by Zinc and Dependent on Lipids

PEDV inhibits HNRNPA3 expression by miR-218-5p to enhance cellular lipid accumulation and promote viral replication

Understanding the Molecular Actions of Spike Glycoprotein in SARS-CoV-2 and Issues of a Novel Therapeutic Strategy for the COVID-19 Vaccine

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