High basal heat-shock protein expression in bats confers resistance to cellular heat/oxidative stress

Chionh, Yok Teng; Cui, Jie; Koh, Javier Yu Peng; Mendenhall, Ian H.; Ng, Justin H. J.; Low, Dolyce H. W.; Itahana, Koji; Irving, Aaron T.; Wang, Lin‐Fa

doi:10.1007/s12192-019-01013-y

Cited by 44 publications

(46 citation statements)

References 75 publications

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“…This could hypothetically lead to the observed G-U and C-A mutation asymmetry. Bats have evolved increased resistance to oxidative stress (Chionh et al, 2019), which could explain why the excess of G-U substitutions is not observed between SARS-CoV-2 and bat coronavirus RaTG13. It is unclear, however, why SARS-CoV-2 is different from SARS-CoV in this regard.…”

Section: Resultsmentioning

confidence: 99%

“…In either scenario, SARS-CoV-2 would be exposed to both a novel evolutionary landscape that affects the fitness of its genetic variants and novel cellular conditions that could affect its mutation rates directly. For example, it is known, that bats have evolved a number of adaptations including superior resistance to oxidative stress (Chionh et al, 2019) that allow them to harbor multiple viruses without getting the corresponding diseases (Schountz et al, 2017). In light of this, we decided to investigate if the relative mutation frequencies in SARS-CoV-2 changed after its transmission to human hosts.…”

Section: Introductionmentioning

confidence: 99%

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Excessive G–U transversions in novel allele variants in SARS-CoV-2 genomes

Panchin¹,

Panchin²

2020

PeerJ

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Background SARS-CoV-2 is a novel coronavirus that causes COVID-19 infection, with a closest known relative found in bats. For this virus, hundreds of genomes have been sequenced. This data provides insights into SARS-CoV-2 adaptations, determinants of pathogenicity and mutation patterns. A comparison between patterns of mutations that occurred before and after SARS-CoV-2 jumped to human hosts may reveal important evolutionary consequences of zoonotic transmission. Methods We used publically available complete genomes of SARS-CoV-2 to calculate relative frequencies of single nucleotide variations. These frequencies were compared with relative substitutions frequencies between SARS-CoV-2 and related animal coronaviruses. A similar analysis was performed for human coronaviruses SARS-CoV and HKU1. Results We found a 9-fold excess of G–U transversions among SARS-CoV-2 mutations over relative substitution frequencies between SARS-CoV-2 and a close relative coronavirus from bats (RaTG13). This suggests that mutation patterns of SARS-CoV-2 have changed after transmission to humans. The excess of G–U transversions was much smaller in a similar analysis for SARS-CoV and non-existent for HKU1. Remarkably, we did not find a similar excess of complementary C–A mutations in SARS-CoV-2. We discuss possible explanations for these observations.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Excessive G–U transversions in novel allele variants in SARS-CoV-2 genomes

Panchin¹,

Panchin²

2020

PeerJ

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“…HSP70, in contrast, is a fundamental anti-inflammatory chaperone of the HSR that may inhibit cytokine storm induced by SARS viruses through binding/degrading p65 subunit of NF-κB [ 79 ], which is needed for a complete inflammatory response and, eventually, a cytokine storm. On the other hand, Chionh and colleagues [ 80 ] have shown that a huge basal expression of HSPs in bats (discussed in detail below) is associated with cell survival to prolonged heat treatment and defense against oxidative stress. From the other point of view, bats are capable of mounting a perpetually activated IFN response [ 81 ] without suffering from any hyperinflammation-induced cytokine storm.…”

Section: Heat Shock Response (Hsr) Fever and The Physiological Resolmentioning

confidence: 99%

Suppressed anti-inflammatory heat shock response in high-risk COVID-19 patients: lessons from basic research (inclusive bats), light on conceivable therapies

et al. 2020

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The major risk factors to fatal outcome in COVID-19 patients, i.e., elderliness and pre-existing metabolic and cardiovascular diseases (CVD), share in common the characteristic of being chronic degenerative diseases of inflammatory nature associated with defective heat shock response (HSR). The molecular components of the HSR, the principal metabolic pathway leading to the physiological resolution of inflammation, is an anti-inflammatory biochemical pathway that involves molecular chaperones of the heat shock protein (HSP) family during homeostasis-threatening stressful situations (e.g., thermal, oxidative and metabolic stresses). The entry of SARS coronaviruses in target cells, on the other hand, aggravates the already-jeopardized HSR of this specific group of patients. In addition, cellular counterattack against virus involves interferon (IFN)-mediated inflammatory responses. Therefore, individuals with impaired HSR cannot resolve virus-induced inflammatory burst physiologically, being susceptible to exacerbated forms of inflammation, which leads to a fatal “cytokine storm”. Interestingly, some species of bats that are natural reservoirs of zoonotic viruses, including SARS-CoV-2, possess an IFN-based antiviral inflammatory response perpetually activated but do not show any sign of disease or cytokine storm. This is possible because bats present a constitutive HSR that is by far (hundreds of times) more intense and rapid than that of human, being associated with a high core temperature. Similarly in humans, fever is a physiological inducer of HSR while antipyretics, which block the initial phase of inflammation, impair the resolution phase of inflammation through the HSR. These findings offer a rationale for the reevaluation of patient care and fever reduction in SARS, including COVID-19.

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“…This could hypothetically lead to the observed G to U and C to A mutation asymmetry. Bats have evolved increased resistance to oxidative stress [8], which could explain why the excess of G to U substitutions is not observed between SARS-CoV-2 and bat coronavirus RaTG13. It is unclear, however, why SARS-CoV-2 is different from SARS-CoV in this regard.…”

Section: Resultsmentioning

confidence: 99%

Peer Review #3 of "Excessive G–U transversions in novel allele variants in SARS-CoV-2 genomes (v0.2)"

2020

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Background. SARS-CoV-2 is a novel coronavirus that causes COVID-19 infection, with a closest known relative found in bats. For this virus, hundreds of genomes have been sequenced. This data provides insights into SARS-CoV-2 adaptations, determinants of pathogenicity and mutation patterns. A comparison between patterns of mutations that occurred before and after SARS-CoV-2 jumped to human hosts may reveal important evolutionary consequences of zoonotic transmission. Methods. We used publically available complete genomes of SARS-CoV-2 to calculate relative frequencies of single nucleotide variations. These frequencies were compared with relative substitutions frequencies between SARS-CoV-2 and related animal coronaviruses. A similar analysis was performed for human coronaviruses SARS-CoV and HKU1. Results. We found a 9-fold excess of G to U transversions among SARS-CoV-2 mutations over relative substitution frequencies between SARS-CoV-2 and a close relative coronavirus from bats (RaTG13). This suggests that mutation patterns of SARS-CoV-2 have changed after transmission to humans. The excess of G to U transversions was much smaller in a similar analysis for SARS-CoV and non-existent for HKU1. Remarkably, we did not find a similar excess of complementary C to A mutations in SARS-CoV-2. We discuss possible explanations for these observations.

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High basal heat-shock protein expression in bats confers resistance to cellular heat/oxidative stress

Cited by 44 publications

References 75 publications

Excessive G–U transversions in novel allele variants in SARS-CoV-2 genomes

Excessive G–U transversions in novel allele variants in SARS-CoV-2 genomes

Suppressed anti-inflammatory heat shock response in high-risk COVID-19 patients: lessons from basic research (inclusive bats), light on conceivable therapies

Peer Review #3 of "Excessive G–U transversions in novel allele variants in SARS-CoV-2 genomes (v0.2)"

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