Infection and chronic disease activate a brain-muscle signaling axis that regulates muscle performance

Yang, Shuo; Tian, Meijie; An, Johnson

doi:10.1101/2020.12.20.423533

Cited by 16 publications

(19 citation statements)

References 128 publications

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“…Notably, these phenotypic findings recapitulate those reported in COVID-19 patients, where respiratory problems, lung injury and myalgia are hallmark features ( Huang et al, 2020 ). In another study, which is still in preprint, SARS-CoV-2 protein Orf3a was also found to be deleterious in Drosophila when expressed in the nervous system leading to reduced lifespan, impaired motor function, cell death and neuroinflammation ( Yang et al, 2020 ). Fatigue and neurological problems are emerging as persistent symptoms of the post-viral syndrome, termed ‘Long COVID’, experienced by several COVID-19 recovering patients ( Shu et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

ACE and ACE2: insights from Drosophila and implications for COVID-19

Herrera

Cauchi

2021

Heliyon

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Angiotensin-converting enzyme (ACE) and its homologue ACE2 are key regulators of the renin-angiotensin system and thereby cardiovascular function through their zinc-metallopeptidase activity on vasoactive peptides. ACE2 also serves as the receptor for the cellular entry of various coronaviruses including the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is responsible for the coronavirus disease 2019 (COVID-19). The unprecedented scale of the COVID-19 pandemic has spurred the use of mammalian models to investigate the SARS-ACE2 relationship and knowledge gained from such research has accelerated development of vaccines and therapeutics. Recent studies have just started to underscore the utility of the fruit fly Drosophila melanogaster as a model system to study virus-host interactions and pathogenicity. Notably, the remarkable existence of catalytically functional ACE and ACE2 orthologues in Drosophila, discovered more than two decades ago, provides a unique opportunity for further developing this model organism to better understand COVID-19 in addition to identifying coronavirus preventative and therapeutic interventions targeting ACE2. Here, we review the studies that revealed crucial insights on the biochemistry and physiology of Ance and Acer , two out of the six Drosophila ACE family members with the greatest homology to human ACE and ACE2. We highlight shared in vivo functions outside of the renin-angiotensin system, which is not conserved in flies. Importantly, we identify knowledge gaps that can be filled by further research and outline ways that can raise Drosophila to a powerful model system to combat SARS-CoV-2 and its threatening vaccine-evading variants.

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Section: Introductionmentioning

confidence: 99%

ACE and ACE2: insights from Drosophila and implications for COVID-19

Herrera

Cauchi

2021

Heliyon

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“…Interestingly, the fecal microbiome of captive macaques increased the citrate cycle (tricarboxylic acid; TCA cycle) and glyoxylate and dicarboxylate metabolism which were suggested to reduce energy consumption and promote energy production 65 . Additionally, the increment of the TCA cycle could oxidize the SCFAs to generate ATP 66 .…”

Section: Discussionmentioning

confidence: 99%

Comparative analysis of oral-gut microbiota between captive and wild long-tailed macaque in Thailand

Sawaswong

Praianantathavorn

Chanchaem

et al. 2021

Sci Rep

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Long-tailed macaques (Macaca fascicularis), distributed in Southeast Asia, are generally used in biomedical research. At present, the expansion of human communities overlapping of macaques’ natural habitat causes human-macaque conflicts. To mitigate this problem in Thailand, the National Primate Research Center of Thailand, Chulalongkorn University (NPRCT-CU), was granted the permit to catch the surplus wild-born macaques and transfer them to the center. Based on the fact that the diets provided and the captive environments were different, their oral-gut microbiota should be altered. Thus, we investigated and compared the oral and fecal microbiome between wild-born macaques that lived in the natural habitats and those transferred to and reared in the NPRCT-CU for 1 year. The results from 16S rRNA high-throughput sequencing showed that the captive macaques had distinct oral-gut microbiota profiles and lower bacterial richness compared to those in wild macaques. The gut of wild macaques was dominated by Firmicutes which is probably associated with lipid absorption and storage. These results implicated the effects of captivity conditions on the microbiome that might contribute to crucial metabolic functions. Our study should be applied to the animal health care program, with respect to microbial functions, for non-human primates.

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“…Despite the fruit fly’s relative limited use to study human viruses and SARS-CoV-2 having arisen just over a year ago, two fly studies have been reported. The bioRxiv preprint server lists one article that used Drosophila to investigate SARS-CoV-2 [ 61 ]. The study focuses on SARS-CoV-2 Orf3a, using the UAS-Gal4 system with tissue-specific drivers, the viral protein was overexpressed in the fly central nervous system ( elav-Gal4 ), photoreceptors ( GMR-Gal4 ), and striated and smooth muscle ( Mef2-Gal4 ).…”

Section: Drosophila In Sars-cov-2 Research To Datementioning

confidence: 99%

“…All flies with photoreceptor Orf3a overexpression showed a rough eye phenotype, indicative of a patterning defect and apoptosis. In contrast to these mild Or3fa-mediated phenotypes, expression in the central nervous system caused partial larval lethality and reduced lifespan, combined with impaired motor function (muscle weakness) and marked abdominal swelling [ 61 ]. At the molecular level, Orf3a induced Caspase-3 cleavage as well as increased expression levels of Toll pathway and immune deficiency (IMD) pathway proteins which are markers of the immune inflammatory response.…”

Section: Drosophila In Sars-cov-2 Research To Datementioning

confidence: 99%

“…Notably, the SARS-CoV-2 genes found to convey highest pathogenicity (i.e., Nsp6 , Orf6 and Orf7a ) in the in vitro human cell culture (HEK 293 T) model were also most pathogenic in our in vivo transgenic flies system [ 23 , 62 ]. In our hands, system-wide overexpression of protein SARS-CoV-2 Orf3a ( Tub-Gal4 ) reduced overall lifespan [ 23 ] but did not increase early lethality (death prior to eclosion) as observed when SARS-CoV-2 Orf3a was overexpressed in the fly central nervous system ( elav-Gal4 ) [ 61 ]. In line with previous studies of human viruses in fly, orthology analysis revealed astounding levels (90%) of conservation for the SARS-CoV-2 virus-host interactome between humans and flies [ 23 ] (Fig.…”

Section: Drosophila In Sars-cov-2 Research To Datementioning

confidence: 99%

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Drosophila, a powerful model to study virus-host interactions and pathogenicity in the fight against SARS-CoV-2

Leemput

Han

2021

Cell Biosci

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The COVID-19 pandemic is having a tremendous impact on humanity. Although COVID-19 vaccines are showing promising results, they are not 100% effective and resistant mutant SARS-CoV-2 strains are on the rise. To successfully fight against SARS-CoV-2 and prepare for future coronavirus outbreaks, it is essential to understand SARS-CoV-2 protein functions, their host interactions, and how these processes convey pathogenicity at host tissue, organ and systemic levels. In vitro models are valuable but lack the physiological context of a whole organism. Current animal models for SARS-CoV-2 research are exclusively mammals, with the intrinsic limitations of long reproduction times, few progeny, ethical concerns and high maintenance costs. These limitations make them unsuitable for rapid functional investigations of virus proteins as well as genetic and pharmacological screens. Remarkably, 90% of the SARS-CoV-2 virus-host interacting proteins are conserved between Drosophila and humans. As a well-established model system for studying human diseases, the fruit fly offers a highly complementary alternative to current mammalian models for SARS-CoV-2 research, from investigating virus protein function to developing targeted drugs. Herein, we review Drosophila’s track record in studying human viruses and discuss the advantages and limitations of using fruit flies for SARS-CoV-2 research. We also review studies that already used Drosophila to investigate SARS-CoV-2 protein pathogenicity and their damaging effects in COVID-19 relevant tissues, as well as studies in which the fly was used as an efficient whole animal drug testing platform for targeted therapeutics against SARS-CoV-2 proteins or their host interacting pathways.

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Infection and chronic disease activate a brain-muscle signaling axis that regulates muscle performance

Cited by 16 publications

References 128 publications

ACE and ACE2: insights from Drosophila and implications for COVID-19

ACE and ACE2: insights from Drosophila and implications for COVID-19

Comparative analysis of oral-gut microbiota between captive and wild long-tailed macaque in Thailand

Drosophila, a powerful model to study virus-host interactions and pathogenicity in the fight against SARS-CoV-2

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