MMS19 and IFIH1 Host Genetic Variants Associate with SARS-CoV-2 Infection in Elderly Residents of Long-Term Care Facilities

Опубликована: Июль 5, 2024

The Coronavirus disease 2019 (COVID-19) pandemic has significantly affected older adults. Identifying host COVID-19 susceptibility genes in elderly populations remains a challenge. Here, we aimed to identify genetic factors influencing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We genotyped 12 single nucleotide polymorphisms (SNPs) previously associated with the innate immune response total of 97 (age >65 years) residents three long-term care facilities located area Barcelona, Spain. Individuals were PCR-tested during SARS-CoV-2 outbreaks between September and November 2020. PCR tests revealed infection 81 residents. Importantly, 16 uninfected remained seronegative until vaccination (January February 2021). After adjusting for sex age, found that two SNPs susceptibility: MMS19 excision repair protein homolog (MMS19)/rs2236575 (p = 0.029) interferon-induced helicase C domain-containing 1 (IFIH1)/rs1990760 0.034). No association was 10 additional SNPs, which included 4 on chromosome gene encoding oligoadenylate synthetase (OAS). Our results indicate IFIH1 variants resistance cohort institutionalized seniors.

Язык: Английский

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The Cryptic Nature of Fe-S Clusters: A Case Study of the Hepatitis B HBx Oncoprotein

Inorganics, Год журнала: 2023, Номер 11(12), С. 475 - 475

Опубликована: Дек. 6, 2023

Fe-S clusters are ubiquitous inorganic cofactors found in proteins across all domains of life, including viruses. Their prevalence stems from their unique redox and structural plasticity that supports functions ranging electron transfer catalysis to stabilization protein structure. Although the ability exchange electrons is often functionally crucial, it can also act as an Achilles heel when these exposed oxidizing conditions, leading degradation. This O2 sensitivity has rendered certain untraceable, particularly nascent isolated under ambient conditions. As a consequence this sensitivity, growing number with roles viral infection have been harbor rather than annotated Zn2+ cofactor. The enigmatic X (HBx) Hepatitis B Virus multifunctional essential for replication development liver disease. HBx defied biochemical characterization over forty years, shown coordinate redox-active cluster represents significant feature establishing its molecular function. present review narrates approaches validate metallocofactor be broadly applied guide uncovering presence non-canonical sequence motifs.

Язык: Английский

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Iron–Sulfur Clusters: Assembly and Biological Roles

Inorganics, Год журнала: 2024, Номер 12(8), С. 216 - 216

Опубликована: Авг. 9, 2024

Iron–sulfur (Fe-S) clusters are critical to a wide range of biological processes, from DNA repair and transcriptional regulation mitochondrial respiration enzymatic catalysis [...]

Язык: Английский

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MMS19 and IFIH1 Host Genetic Variants Associate with SARS-CoV-2 Infection in Elderly Residents of Long-Term Care Facilities

COVID, Год журнала: 2024, Номер 4(8), С. 1245 - 1252

Опубликована: Авг. 7, 2024

The coronavirus disease 2019 (COVID-19) pandemic has significantly affected older adults. Identifying host COVID-19 susceptibility genes in elderly populations remains a challenge. Here, we aimed to identify genetic factors influencing the severe acute respiratory syndrome 2 (SARS-CoV-2) infection. We genotyped 12 single-nucleotide polymorphisms (SNPs) previously associated with innate immune response total of 97 (age > 65 years) residents three long-term care facilities located Barcelona, Spain. Individuals were PCR-tested during SARS-CoV-2 outbreaks between September and November 2020. PCR tests revealed infections 81 residents. Importantly, 16 uninfected remained seronegative until vaccination (January February 2021). After adjusting for sex age, found that two SNPs infection susceptibility—MMS19 nucleotide excision repair protein homolog (MMS19)/rs2236575 (p = 0.029) interferon-induced helicase C domain-containing 1 (IFIH1)/rs1990760 0.034). No association was 10 additional SNPs, which included 4 on chromosome gene encoding oligoadenylate synthetase (OAS). Our results indicate MMS19/rs2236575_A IFIH1/rs1990760_TC variants resistance cohort institutionalized seniors.

Язык: Английский

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Guardians of the Genome: Iron–Sulfur Proteins in the Nucleus

Inorganics, Год журнала: 2024, Номер 12(12), С. 316 - 316

Опубликована: Дек. 6, 2024

Iron–sulfur (Fe-S) clusters are essential cofactors found in many proteins the mitochondria, cytosol, and nucleus of cell. These versatile may undergo reversible oxidation–reduction reactions to enable electron transfers; they be structural confer stability a folded protein; regulatory transduce an iron signal that alters function or recipient protein. Of nearly 70 described mammalian cells bind Fe-S clusters, about half localize exclusively partially nucleus, where required for DNA replication repair, telomere maintenance, transcription, mitosis, cell cycle control. Most nuclear cluster interact with DNA, including polymerases, primase, helicases, glycosylases. However, specific roles enzymatic activities these their interplay remain matter debate. Defects metallation cause genome instability alter regulation division proliferation, which hallmarks various genetic diseases cancers. Here, we provide inventory cluster-binding discuss types, binding sites, process acquisition, potential proteins. questions unresolved. We highlight critical gaps our understanding delivery client proteins, mechanistic play enzymes. Taken together, this review brings focus human as hotspot aims inspire new research on metabolism maintenance integrity.

Язык: Английский

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