The Oxysterol 7-Ketocholesterol Reduces Zika Virus Titers in Vero Cells and Human Neurons

Willard, Katherine A.; Elling, Christina L.; Stice, Steven L.; Brindley, Melinda A.

doi:10.3390/v11010020

Cited by 55 publications

(21 citation statements)

References 44 publications

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“…Specifically, elevated intracellular levels of 25‐HC, have been previously shown to reduce infectivity by several members of the coronaviridae, filoviridae (eg, Ebola virus), and flaviviridae (eg, Zika and hepatitis C viruses) 54‐57 . Similarly, increased intracellular levels of 7‐KC have been shown to interfere with viral maturation, and subsequent budding and release from host cells 58 . While the precise mechanism(s) underlying their antiviral activities remain a subject of ongoing debate, these oxysterols have been shown to perturb the normal trafficking of cholesterol, such that they replace the latter within the lipid rafts, altering their properties, which impairs subsequent viral entry, endocytic transport of viral particles, and their eventual fusion intracellularly 56,59 …”

Section: The Oxysterols That Accumulate In Npc Possess Potent Antivirmentioning

confidence: 99%

The lysosome: A potential juncture between SARS‐CoV‐2 infectivity and Niemann‐Pick disease type C, with therapeutic implications

et al. 2020

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Drug repurposing is potentially the fastest available option in the race to identify safe and efficacious drugs that can be used to prevent and/or treat COVID‐19. By describing the life cycle of the newly emergent coronavirus, SARS‐CoV‐2, in light of emerging data on the therapeutic efficacy of various repurposed antimicrobials undergoing testing against the virus, we highlight in this review a possible mechanistic convergence between some of these tested compounds. Specifically, we propose that the lysosomotropic effects of hydroxychloroquine and several other drugs undergoing testing may be responsible for their demonstrated in vitro antiviral activities against COVID‐19. Moreover, we propose that Niemann‐Pick disease type C (NPC), a lysosomal storage disorder, may provide new insights into potential future therapeutic targets for SARS‐CoV‐2, by highlighting key established features of the disorder that together result in an “unfavorable” host cellular environment that may interfere with viral propagation. Our reasoning evolves from previous biochemical and cell biology findings related to NPC, coupled with the rapidly evolving data on COVID‐19. Our overall aim is to suggest that pharmacological interventions targeting lysosomal function in general, and those particularly capable of reversibly inducing transient NPC‐like cellular and biochemical phenotypes, constitute plausible mechanisms that could be used to therapeutically target COVID‐19.

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Section: The Oxysterols That Accumulate In Npc Possess Potent Antivirmentioning

confidence: 99%

The lysosome: A potential juncture between SARS‐CoV‐2 infectivity and Niemann‐Pick disease type C, with therapeutic implications

et al. 2020

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“…Viral genomes were detected as previously described (Willard et al, 2019). Briefly, dissected mosquito midguts were collected in pools of five, and viral RNA was isolated using the Zymo Quick-RNA Viral Kit (Zymo, Irvine, CA, United States).…”

Section: Viral Genome Quantificationmentioning

confidence: 99%

Temperature Dramatically Shapes Mosquito Gene Expression With Consequences for Mosquito–Zika Virus Interactions

et al. 2020

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Vector-borne flaviviruses are emerging threats to human health. For successful transmission, the virus needs to efficiently enter mosquito cells and replicate within and escape several tissue barriers while mosquitoes elicit major transcriptional responses to flavivirus infection. This process will be affected not only by the specific mosquitopathogen pairing but also by variation in key environmental variables such as temperature. Thus far, few studies have examined the molecular responses triggered by temperature and how these responses modify infection outcomes, despite substantial evidence showing strong relationships between temperature and transmission in a diversity of systems. To define the host transcriptional changes associated with temperature variation during the early infection process, we compared the transcriptome of mosquito midgut samples from mosquitoes exposed to Zika virus (ZIKV) and nonexposed mosquitoes housed at three different temperatures (20, 28, and 36 • C). While the high-temperature samples did not show significant changes from those with standard rearing conditions (28 • C) 48 h post-exposure, the transcriptome profile of mosquitoes housed at 20 • C was dramatically different. The expression of genes most altered by the cooler temperature involved aspects of blood-meal digestion, ROS metabolism, and mosquito innate immunity. Further, we did not find significant differences in the viral RNA copy number between 24 and 48 h post-exposure at 20 • C, suggesting that ZIKV replication is limited by cold-induced changes to the mosquito midgut environment. In ZIKV-exposed mosquitoes, vitellogenin, a lipid carrier protein, was most up-regulated at 20 • C. Our results provide a deeper understanding of the temperature-triggered transcriptional changes in Aedes aegypti and can be used to further define the molecular mechanisms driven by environmental temperature variation.

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“…Viral genomes were detected as previously described (Willard et al, 2019). Briefly dissected mosquito midguts were collected in pools of 5 and viral RNA was isolated using the Zymo Quick-RNA™ Viral Kit (Zymo, Irvine, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

Temperature Dramatically Shapes Mosquito Gene Expression with Consequences for Mosquito-Zika Virus Interactions

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et al. 2019

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5Vector-borne flaviviruses are emerging threats to human health. For successful 3 6 transmission, the virus needs to efficiently enter mosquito cells, replicate within, and 3 7 escape several tissue barriers while mosquitoes elicit major transcriptional responses to 3 8 flavivirus infection. This process will not only be affected by the specific mosquito-3 9 pathogen pairing, but also variation in key environmental variables such as temperature. 4 0 Thus far, few studies have examined the molecular responses triggered by temperature 4 1 and how these responses modify infection outcomes despite substantial evidence 4 2 showing strong relationships between temperature and transmission in a diversity of 4 3 systems. To define the host transcriptional changes associated with temperature 4 4 variation during the early infection process, we compared the transcriptome of mosquito 4 5midgut samples from mosquitoes exposed to Zika virus (ZIKV) and non-exposed 4 6 mosquitoes housed at three different temperatures (20, 28, and 36°C). While the high 4 7 temperature samples did not have significant changes from standard rearing conditions 4 8 These temperature constraints on infection are likely regulated through different 1 3 2 mechanisms. Temperature variation in general could profoundly impact arbovirus

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The Oxysterol 7-Ketocholesterol Reduces Zika Virus Titers in Vero Cells and Human Neurons

Cited by 55 publications

References 44 publications

The lysosome: A potential juncture between SARS‐CoV‐2 infectivity and Niemann‐Pick disease type C, with therapeutic implications

The lysosome: A potential juncture between SARS‐CoV‐2 infectivity and Niemann‐Pick disease type C, with therapeutic implications

Temperature Dramatically Shapes Mosquito Gene Expression With Consequences for Mosquito–Zika Virus Interactions

Temperature Dramatically Shapes Mosquito Gene Expression with Consequences for Mosquito-Zika Virus Interactions

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