A global lipid map defines a network essential for Zika virus replication

Leier, Hans C.; Weinstein, Jules B; Kyle, Jennifer; Lee, Joon‐Yong; Bramer, Lisa; Stratton, Kelly G.; Kempthorne, Douglas; Navratil, Aaron R.; Tafesse, Endale G.; Hornemann, Thorsten; Messer, William B.; Dennis, Edward A.; Metz, Thomas O.; Barklis, Eric; Tafesse, Fikadu G.

doi:10.1038/s41467-020-17433-9

Cited by 55 publications

(67 citation statements)

References 123 publications

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“…The sphingolipid ceramide is required for vesicle biogenesis, an important process during flaviviral replication, and may be generated by the degradation of sphingomyelin ( Trajkovic et al, 2008 ). It was shown that both WNV and ZIKV increase cellular sphingolipid levels, and blocking the conversion from sphingomyelin to ceramide inhibits their replication ( Martín-Acebes et al, 2014 ; Martín-Acebes et al, 2016 ; Leier et al, 2020 ). Using ZIKV, it was also demonstrated that ceramide is redistributed to replication membranes, suggesting their involvement in flaviviral vesicle formation ( Leier et al, 2020 ).…”

Section: Intracellular Growthmentioning

confidence: 99%

“…It was shown that both WNV and ZIKV increase cellular sphingolipid levels, and blocking the conversion from sphingomyelin to ceramide inhibits their replication ( Martín-Acebes et al, 2014 ; Martín-Acebes et al, 2016 ; Leier et al, 2020 ). Using ZIKV, it was also demonstrated that ceramide is redistributed to replication membranes, suggesting their involvement in flaviviral vesicle formation ( Leier et al, 2020 ). Patients infected with flaviviruses exhibit lipidomic changes, such as dysregulated sphingolipids levels and perturbed lipid metabolic pathways, pointing to a critical process during viral infection ( Cui et al, 2013 ; Melo et al, 2017 ).…”

Section: Intracellular Growthmentioning

confidence: 99%

“…By studying levels of metabolites, researchers can interrogate thousands of molecular changes including those involved in lipid metabolism. Lipidomics has already been applied for several vector-borne pathogens and has been instrumental in understanding host-pathogen interactions ( Blaho et al, 2009 ; Perera et al, 2012 ; Cui et al, 2013 ; Gulati et al, 2015 ; Gardinassi et al, 2017 ; Gazos-Lopes et al, 2017 ; Melo et al, 2016 ; Melo et al, 2017 ; Chotiwan et al, 2018 ; Cordy et al, 2019 ; Vial et al, 2019 ; Leier et al, 2020 ); however, its further implementation with hypothesis-driven research may uncover universal mechanisms shared by several microbes. Additionally, the rise of cutting-edge technologies, such as single-cell metabolomics and mass spectrometry imaging, allows researchers to take a systems biology approach to answering metabolic questions.…”

Section: Conclusion and Perspectivementioning

confidence: 99%

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Lipid hijacking: A unifying theme in vector-borne diseases

O’Neal

Butler

Rolandelli

et al. 2020

eLife

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Vector-borne illnesses comprise a significant portion of human maladies, representing 17% of global infections. Transmission of vector-borne pathogens to mammals primarily occurs by hematophagous arthropods. It is speculated that blood may provide a unique environment that aids in the replication and pathogenesis of these microbes. Lipids and their derivatives are one component enriched in blood and are essential for microbial survival. For instance, the malarial parasite Plasmodium falciparum and the Lyme disease spirochete Borrelia burgdorferi, among others, have been shown to scavenge and manipulate host lipids for structural support, metabolism, replication, immune evasion, and disease severity. In this Review, we will explore the importance of lipid hijacking for the growth and persistence of these microbes in both mammalian hosts and arthropod vectors.

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Section: Intracellular Growthmentioning

confidence: 99%

Section: Intracellular Growthmentioning

confidence: 99%

Section: Conclusion and Perspectivementioning

confidence: 99%

See 1 more Smart Citation

Lipid hijacking: A unifying theme in vector-borne diseases

O’Neal

Butler

Rolandelli

et al. 2020

eLife

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“…After aspiration of the PBS, cell pellets were resuspended in 1 ml of ice-cold methanol and stored at −80 °C. Using a modified Folch extraction ( 80 , 81 ), chloroform and water were added to samples for a final ratio of 8:4:3 chloroform:methanol:water. The samples were vortexed to mix, chilled on ice for 5 min, and then vortexed again.…”

Section: Methodsmentioning

confidence: 99%

Ceramide synthase 2 deletion decreases the infectivity of HIV-1

Barklis

Alfadhli

Kyle

et al. 2021

Journal of Biological Chemistry

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The lipid composition of HIV-1 virions is enriched in sphingomyelin (SM), but the roles that SM or other sphingolipids (SLs) might play in the HIV-1 replication pathway have not been elucidated. In human cells, SL levels are regulated by ceramide synthase (CerS) enzymes that produce ceramides, which can be converted to SMs, hexosylceramides, and other SLs. In many cell types, CerS2, which catalyzes the synthesis of very long chain ceramides, is the major CerS. We have examined how CerS2 deficiency affects the assembly and infectivity of HIV-1. As expected, we observed that very long chain ceramide, hexosylceramide, and SM were reduced in CerS2 knockout cells. CerS2 deficiency did not affect HIV-1 assembly or the incorporation of the HIV-1 envelope (Env) protein into virus particles, but it reduced the infectivites of viruses produced in the CerS2-deficient cells. The reduced viral infection levels were dependent on HIV-1 Env, since HIV-1 particles that were pseudotyped with the vesicular stomatitis virus glycoprotein did not exhibit reductions in infectivity. Moreover, cell–cell fusion assays demonstrated that the functional defect of HIV-1 Env in CerS2-deficient cells was independent of other viral proteins. Overall, our results indicate that the altered lipid composition of CerS2-deficient cells specifically inhibit the HIV-1 Env receptor binding and/or fusion processes.

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“…Host lipid remodeling is also observed in vertebrate infection by arboviruses to support their replication ( Ng et al, 2008 ; Fernández de Castro et al, 2016 ; Leier et al, 2020 ). Similar reprogramming events have already been shown in vector cells ( Perera et al, 2012 ; O’neal et al, 2020 ).…”

Section: Blood Digestion and Metabolic Signalingmentioning

confidence: 99%

Non-immune Traits Triggered by Blood Intake Impact Vectorial Competence

et al. 2021

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Blood-feeding arthropods are considered an enormous public health threat. They are vectors of a plethora of infectious agents that cause potentially fatal diseases like Malaria, Dengue fever, Leishmaniasis, and Lyme disease. These vectors shine due to their own physiological idiosyncrasies, but one biological aspect brings them all together: the requirement of blood intake for development and reproduction. It is through blood-feeding that they acquire pathogens and during blood digestion that they summon a collection of multisystemic events critical for vector competence. The literature is focused on how classical immune pathways (Toll, IMD, and JAK/Stat) are elicited throughout the course of vector infection. Still, they are not the sole determinants of host permissiveness. The dramatic changes that are the hallmark of the insect physiology after a blood meal intake are the landscape where a successful infection takes place. Dominant processes that occur in response to a blood meal are not canonical immunological traits yet are critical in establishing vector competence. These include hormonal circuitries and reproductive physiology, midgut permeability barriers, midgut homeostasis, energy metabolism, and proteolytic activity. On the other hand, the parasites themselves have a role in the outcome of these blood triggered physiological events, consistently using them in their favor. Here, to enlighten the knowledge on vector–pathogen interaction beyond the immune pathways, we will explore different aspects of the vector physiology, discussing how they give support to these long-dated host–parasite relationships.

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A global lipid map defines a network essential for Zika virus replication

Cited by 55 publications

References 123 publications

Lipid hijacking: A unifying theme in vector-borne diseases

Lipid hijacking: A unifying theme in vector-borne diseases

Ceramide synthase 2 deletion decreases the infectivity of HIV-1

Non-immune Traits Triggered by Blood Intake Impact Vectorial Competence

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