Viruses and phospholipids: Friends and foes during infection

Rattay, Stephanie; Hufbauer, Martin; Hoboth, Peter; Sztacho, Martin; Akgül, Baki

doi:10.1002/jmv.28658

Cited by 10 publications

(3 citation statements)

References 107 publications

(232 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The biological importance of membrane lipids has long been recognised, both as barriers to infection and, once cleaved, as circulating or locally acting modulators of the immune response to pathogens. [1][2][3] While perturbation of the serum lipidome by infections is well documented, [4][5][6][7][8] attention has focused on high abundance lipids such as phospholipids, ceramides and sphingomyelins. This has been true also in COVID- 19 where the high abundance lipidome has been implicated in prognosis, 9 pathogenesis 10 and disease severity.…”

Section: Introductionmentioning

confidence: 99%

Deep phenotyping of the lipidomic response in COVID‐19 and non‐COVID‐19 sepsis

Meng,

Sengupta,

Ricciotti

et al. 2023

Clinical & Translational Med

View full text Add to dashboard Cite

BackgroundLipids may influence cellular penetrance by viral pathogens and the immune response that they evoke. We deeply phenotyped the lipidomic response to SARs‐CoV‐2 and compared that with infection with other pathogens in patients admitted with acute respiratory distress syndrome to an intensive care unit (ICU).MethodsMass spectrometry was used to characterise lipids and relate them to proteins, peripheral cell immunotypes and disease severity.ResultsCirculating phospholipases (sPLA2, cPLA2 (PLA2G4A) and PLA2G2D) were elevated on admission in all ICU groups. Cyclooxygenase, lipoxygenase and epoxygenase products of arachidonic acid (AA) were elevated in all ICU groups compared with controls. sPLA2 predicted severity in COVID‐19 and correlated with TxA2, LTE4 and the isoprostane, iPF2α‐III, while PLA2G2D correlated with LTE4. The elevation in PGD2, like PGI2 and 12‐HETE, exhibited relative specificity for COVID‐19 and correlated with sPLA2 and the interleukin‐13 receptor to drive lymphopenia, a marker of disease severity. Pro‐inflammatory eicosanoids remained correlated with severity in COVID‐19 28 days after admission. Amongst non‐COVID ICU patients, elevations in 5‐ and 15‐HETE and 9‐ and 13‐HODE reflected viral rather than bacterial disease. Linoleic acid (LA) binds directly to SARS‐CoV‐2 and both LA and its di‐HOME products reflected disease severity in COVID‐19. In healthy marines, these lipids rose with seroconversion. Eicosanoids linked variably to the peripheral cellular immune response. PGE2, TxA2 and LTE4 correlated with T cell activation, as did PGD2 with non‐B non‐T cell activation. In COVID‐19, LPS stimulated peripheral blood mononuclear cell PGF2α correlated with memory T cells, dendritic and NK cells while LA and DiHOMEs correlated with exhausted T cells. Three high abundance lipids – ChoE 18:3, LPC‐O‐16:0 and PC‐O‐30:0 – were altered specifically in COVID. LPC‐O‐16:0 was strongly correlated with T helper follicular cell activation and all three negatively correlated with multi‐omic inflammatory pathways and disease severity.ConclusionsA broad based lipidomic storm is a predictor of poor prognosis in ARDS. Alterations in sPLA2, PGD2 and 12‐HETE and the high abundance lipids, ChoE 18:3, LPC‐O‐16:0 and PC‐O‐30:0 exhibit relative specificity for COVID‐19 amongst such patients and correlate with the inflammatory response to link to disease severity.

show abstract

Section: Introductionmentioning

confidence: 99%

Deep phenotyping of the lipidomic response in COVID‐19 and non‐COVID‐19 sepsis

Meng,

Sengupta,

Ricciotti

et al. 2023

Clinical & Translational Med

View full text Add to dashboard Cite

show abstract

“…We super-resolved here for the first time within the context of human clinical FFPE tissue the multiple nuclear antigens, specifically the molecular anatomy of NS and its associated nPI(4,5)P2 pool. Nanoscale protein and lipid interactions execute specific cellular functions and their impairment or hijacking by pathogens leads to the development and progression of disease (Rattay et al, 2023). Here, we quantitatively showed that, compared with healthy skin nuclei, the staining of SON + NS-associated pool of nPI(4,5)P2 is increased in nuclei in HPV-induced wart.…”

Section: Discussionmentioning

confidence: 72%

Quantitative super-resolution microscopy reveals the differences in the nanoscale distribution of nuclear phosphatidylinositol 4,5-bisphosphate in human healthy skin and skin warts

Hoboth

Sztacho

Quaas

et al. 2023

Front. Cell Dev. Biol.

Self Cite

View full text Add to dashboard Cite

Introduction: Imaging of human clinical formalin-fixed paraffin-embedded (FFPE) tissue sections provides insights into healthy and diseased states and therefore represents a valuable resource for basic research, as well as for diagnostic and clinical purposes. However, conventional light microscopy does not allow to observe the molecular details of tissue and cell architecture due to the diffraction limit of light. Super-resolution microscopy overcomes this limitation and provides access to the nanoscale details of tissue and cell organization.Methods: Here, we used quantitative multicolor stimulated emission depletion (STED) nanoscopy to study the nanoscale distribution of the nuclear phosphatidylinositol 4,5-bisphosphate (nPI(4,5)P2) with respect to the nuclear speckles (NS) marker SON.Results: Increased nPI(4,5)P2 signals were previously linked to human papillomavirus (HPV)-mediated carcinogenesis, while NS-associated PI(4,5)P2 represents the largest pool of nPI(4,5)P2 visualized by staining and microscopy. The implementation of multicolor STED nanoscopy in human clinical FFPE skin and wart sections allowed us to provide here the quantitative evidence for higher levels of NS-associated PI(4,5)P2 in HPV-induced warts compared to control skin.Discussion: These data expand the previous reports of HPV-induced increase of nPI(4,5)P2 levels and reveal for the first time the functional, tissue-specific localization of nPI(4,5)P2 within NS in clinically relevant samples. Moreover, our approach is widely applicable to other human clinical FFPE tissues as an informative addition to the classical histochemistry.

show abstract

“…The biological importance of membrane lipids has long been recognized, both as barriers to infection and, once cleaved, as circulating or locally acting modulators of the immune response to pathogens (1)(2)(3). While perturbation of the serum lipidome by infections is well-documented (4 -8), attention has focused on high abundance lipids such as phospholipids, ceramides and sphingomyelins.…”

Section: Introductionmentioning

confidence: 99%

Deep Phenotyping of the Lipidomic Response in COVID and non-COVID Sepsis

Meng,

Sengupta,

Ricciotti

et al. 2023

Preprint

View full text Add to dashboard Cite

Lipids may influence cellular penetrance by pathogens and the immune response that they evoke. Here we find broad based lipidomic storm driven predominantly by secretory (s) phospholipase A2 (sPLA2) dependent eicosanoid production occurs in patients with sepsis of viral and bacterial origin and relates to disease severity in COVID-19. Elevations in the cyclooxygenase (COX) products of arachidonic acid (AA), PGD2 and PGI2, and the AA lipoxygenase (LOX) product, 12-HETE, and a reduction in the high abundance lipids, ChoE 18:3, LPC O-16:0 and PC-O-30:0 exhibit relative specificity for COVID-19 amongst such patients, correlate with the inflammatory response and link to disease severity. Linoleic acid (LA) binds directly to SARS-CoV-2 and both LA and its di-HOME products reflect disease severity in COVID-19. AA and LA metabolites and LPC-O-16:0 linked variably to the immune response. These studies yield prognostic biomarkers and therapeutic targets for patients with sepsis, including COVID-19. An interactive purpose built interactive network analysis tool was developed, allowing the community to interrogate connections across these multiomic data and generate novel hypotheses.

show abstract

Viruses and phospholipids: Friends and foes during infection

Cited by 10 publications

References 107 publications

Deep phenotyping of the lipidomic response in COVID‐19 and non‐COVID‐19 sepsis

Deep phenotyping of the lipidomic response in COVID‐19 and non‐COVID‐19 sepsis

Quantitative super-resolution microscopy reveals the differences in the nanoscale distribution of nuclear phosphatidylinositol 4,5-bisphosphate in human healthy skin and skin warts

Deep Phenotyping of the Lipidomic Response in COVID and non-COVID Sepsis

Contact Info

Product

Resources

About