A perusal through historical and current publications worth mentioning.
This post connects to other posts of mine, including:
‘Enthusiasm + Wrecking Ball’ [molecular mechanisms in Zika microcephaly];
How is a Brick like a Bat? [2012 list of lab tools to target and kill cells including Heat Shock Protein (HSP), nano]
Bullous Blisters after Spike [HSP, nano, Spike molecular mimicry, bullous disease, Guillain-Barré, other pathologies]
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Leaping to Associations: follow the science
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2020: SARS-CoV-2 and Guillain-Barré syndrome: molecular mimicry with human heat shock proteins as potential pathogenic mechanism
Lucchese G, Flöel A.Cell Stress Chaperones. 2020 Sep;25(5):731-735. doi: 10.1007/s12192-020-01145-6.
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2016: Nearly 2 decades of heat-shock protein 90- targeted drug discovery
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2012: Heat shock protein as an established target to kill cells
Cancer: Tumor Iron Metabolism, Mitochondrial Dysfunction and Tumor Immunosuppression; “A Tight Partnership—Was Warburg Correct?”
Table: Elliott RL and Head JF. 2012. DOI: 10.4236/jct.2012.34039 Covered in my other posts.
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(Heat Shock Protein 70) HSP70 Copurifies with Zika Virus Particles
Khachatoorian R, Cohn W, Buzzanco A, Riahi R, Arumugaswami V, Dasgupta A, Whitelegge JP, French SW.Virology. 2018 Sep;522:228-233. doi: 10.1016/j.virol.2018.07.009. Epub 2018 Jul 25.PMID: 30053656
“In this study, we sought to identify potential host proteins interacting with ZIKV particles to gain better insights into viral infectivity … Incubating viral particles with antibody against HSP70 indeed significantly reduced viral infectivity … Preincubating cells with recombinant HSP70 also decreased viral infectivity. Knockdown and inhibition of HSP70 also significantly diminished viral production. These results implicate HSP70 in the pathogenesis of ZIKV and identify HSP70 as a potential host therapeutic target against ZIKV infection.”
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Zika E glycan loop region and Guillain-Barré syndrome-related proteins: A possible molecular mimicry to be taken in account for vaccine development.
Lebeau G, Frumence E, Turpin J, Begue F, Hoarau JJ, Gadea G, Krejbich-Trotot P, Desprès P, Viranaicken W.Vaccines (Basel). 2021 Mar 19;9(3):283. doi: 10.3390/vaccines9030283.PMID: 33808706
“The neurological complications of infection by the mosquito-borne Zika virus (ZIKV) include Guillain-Barré syndrome (GBS), an acute inflammatory demyelinating polyneuritis. GBS was first associated with recent ZIKV epidemics caused by the emergence of the ZIKV Asian lineage in South Pacific.”
(South Pacific: see Yap Islands, Micronesia info below. Labs use viral bases (as seen with Corona and Adeno studies) then add additional proteins of interest - such as Heat Shock Protein, according to Rochani et al. and Elliot and Head in the studies mentioned above…)
“Here, we hypothesize that ZIKV-associated GBS relates to a molecular mimicry between viral envelope E (E) protein and neural proteins involved in GBS. The analysis of the ZIKV epidemic strains showed that the glycan loop (GL) region of the E protein includes an IVNDT motif which is conserved in voltage-dependent L-type calcium channel subunit alpha-1C (Cav1.2) and Heat Shock 70 kDa protein 12A (HSP70 12A). Both VSCC-alpha 1C and HSP70 12A belong to protein families which have been associated with neurological autoimmune diseases in central nervous system. The purpose of our in silico analysis is to point out that IVNDT motif of ZIKV E-GL region should be taken in consideration for the development of safe and effective anti-Zika vaccines by precluding the possibility of adverse neurologic events including autoimmune diseases such as GBS through a potent mimicry with Heat Shock 70 kDa protein 12A.”
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Remember “potent mimicry with Heat Shock 70” for info below…
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Not today’s topic, but speaking of L-type calcium channels…..
Inhibitors of L-Type Calcium Channels Show Therapeutic Potential for Treating SARS-CoV-2 Infections by Preventing Virus Entry and Spread
Straus MR, Bidon MK, Tang T, Jaimes JA, Whittaker GR, Daniel S. ACS Infect Dis. 2021 Oct 8;7(10):2807-2815. doi: 10.1021/acsinfecdis.1c00023.
“…In an attempt to accelerate drug repurposing, we tested a panel of L-type calcium channel blocker (CCB) drugs … to determine whether they would inhibit SARS-CoV-2 infection in cell culture. All the CCBs tested showed varying degrees of inhibition … Further studies with pseudotyped particles displaying the SARS-CoV-2 spike protein suggested that inhibition occurs at the level of virus entry. …”
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Leaping to the Yap Islands, Micronesia
Wikipedia 2022: “In 2007, physicians in the Yap Islands reported to the CDC… a significant finding… a household survey… Prior to the Yap Islands outbreak, no previous outbreaks of Zika virus had ever been reported and only 14 cases had been documented since the virus was first isolated in 1947… Aedes aegypti has been recognized as the vector of Zika virus.”
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Leaping back to the lab: Aedes aegypti
2002:
Harris A, et al. Successful suppression of a field mosquito population by sustained release of engineered male mosquitões. Nature Biotch. 2002;30:828–830. doi: 10.1038/nbt.2350.
2007:
Phuc HK, et al. Late-acting dominant lethal genetic systems and mosquito control. BMC Biol. 2007;5:11. doi: 10.1186/1741-7007-5-11.
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2015, Aedes aegypti Brazil:
Carvalho DO, et al. Suppression of a field population of Aedes aegypti in Brazil by sustained release of transgenic male mosquitoes. PLoS Negl Trop Dis. 2015;9(7):e0003864. doi: 10.1371/journal.pntd.0003864. - PubMed
Described by Garziera L, et al. (Effect of interruption of over-flooding releases of transgenic mosquitoes over wild population of Aedes aegypti: two case studies in Brazil. doi: 10.1111/eea.12618. - DOI):
“The RIDL (Release of Insects with Dominant Lethality) strategy … involves the release of non-sterile males… (Wilke et al., 2009; Black et al., 2011; Alphey, 2014). RIDL uses a transgenic approach for the dissemination of a self-lethal gene to the offspring, which then dies before reaching adulthood (Alphey, 2002; Phuc et al., 2007). The Cayman Islands and Brazil were the first areas where mosquito suppression occurred (Harris et al., 2012; Carvalho et al., 2015). The first study released transgenic males of an Ae. aegypti strain (OX513A) in an open field in the Cayman Islands to achieve population suppression (Harris et al., 2012) – 80% reduction … was achieved. This positive result led to a parallel initiative to scale up the experiment using the same strain to evaluate the effects in a Brazilian environment: the local Ae. aegypti wild population was reduced by 81%… (Carvalho et al., 2015).”
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2017, Aedes aegypti Brazil + Zika:
Costa-da-Silva AL. Laboratory strains of Aedes aegypti are competent to Brazilian Zika virus. PLoS One. 2017;12:e0171951. doi: 10.1371/journal.pone.0171951.
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“Potent mimicry with Heat Shock 70”:
Genomic sequences derived from Aedes aegypti HSP70: Transgenic expression / inducible promoters / RNA transgenes / Genetic sterility
2011: Robust heat-inducible gene expression by two endogenous hsp70-derived promoters in transgenic Aedes aegypti
T. L. G. Carpenetti,A. Aryan,K. M. Myles,Z. N. Adelman. https://doi.org/10.1111/j.1365-2583.2011.01116.x
“Aedes aegypti is an important vector of the viruses that cause dengue fever, dengue haemorrhagic fever and yellow fever. Reverse genetic approaches to the study of gene function in this mosquito have been limited by the lack of a robust inducible promoter to allow precise temporal control over a protein-encoding or hairpin RNA transgene. Likewise, investigations into the molecular and biochemical basis of vector competence would benefit from the ability to activate an antipathogen molecule at specific times during infection. We have characterized the ability of genomic sequences derived from two Ae.aegypti heat shock protein 70 (hsp70) genes to drive heat-inducible expression of a reporter in both transient and germline transformation contexts. AaHsp70-luciferase transcripts accumulated specifically after heat shock, and displayed a pattern of rapid induction and decay similar to endogenous AaHsp70 genes. … The AaHsp70 promoters described could be valuable for gene function studies as well as for the precise timing of the expression of antipathogen molecules.
…Current efforts to control Ae. aegypti populations … have not yet been sufficient ... Genetic control strategies are being developed … with a number of recent reports describing the development of novel female-killing or pathogen-resistant transgenic mosquito strains (Fu et al., 2010; Kokoza et al., 2010; Isaacs et al., 2011; Meredith et al., 2011; Wise de Valdez et al., 2011).
The generation of pathogen-resistant, genetically sterile or female-killing transgenic mosquitoes depends upon the ability to drive the expression of one or more foreign genes ... Likewise, basic research studies addressing questions of gene function using ectopic expression or gene knockdown must often be precisely timed in order to avoid developmentally disruptive phenotypes. A wide range of promoter elements have been characterized and utilized to drive transgene expression or gene knockdown in Ae. aegypti, including … ovary-specific vitellogenin receptor and nanos promoters (Cho et al., 2006; Adelman et al., 2007), the testes-specific β2 tubulin promoter (Smith et al., 2007)….”
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2016: “Of course, the remaining question is ‘Why?’”
April 12, 2016. Above image AFP, text: David K. Li News Corp Australian Network. https://www.adelaidenow.com.au/lifestyle/health/zika-virus-tied-to-brain-disease-similar-to-multiple-sclerosis/news-story/