ABSTRACT
We are currently facing a pandemic of COVID-19, caused by a spillover from an animal-originating coronavirus to humans occurring in the Wuhan region of China in December 2019. From China, the virus has spread to 188 countries and regions worldwide, reaching the Sahel region on March 2, 2020. Since whole genome sequencing (WGS) data is very crucial to understand the spreading dynamics of the ongoing pandemic, but only limited sequencing data is available from the Sahel region to date, we have focused our efforts on generating the first Malian sequencing data available. Screening 217 Malian patient samples for the presence of SARS-CoV-2 resulted in 38 positive isolates, from which 21 whole genome sequences were generated. Our analysis shows that both the early A (19B) and the later observed B (20A/C) clade are present in Mali, indicating multiple and independent introductions of SARS-CoV-2 to the Sahel region.
Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/epidemiology , Genome, Viral/genetics , Pneumonia, Viral/epidemiology , RNA, Viral/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Betacoronavirus/isolation & purification , COVID-19 , Child , Child, Preschool , Female , Genetic Variation/genetics , Genomics , Humans , Male , Mali/epidemiology , Middle Aged , Pandemics , Phylogeny , SARS-CoV-2 , Whole Genome Sequencing , Young AdultABSTRACT
Availability of methionine is known to modulate the rate of aging in model organisms, best illustrated by the observation that dietary methionine restriction extends the lifespan of rodents. However, the underlying mechanisms are incompletely understood. In eukaryotic cells, methionine can be converted to cysteine through the reverse transsulfuration pathway thereby modulating intracellular methionine availability. Whereas previous results obtained in yeast and fruit flies suggest that alterations in the reverse transsulfuration pathway modulate the rate of aging, it is not known whether this function is conserved in evolution. Here we show that depletion of cystathionine beta synthase (CBS), a rate limiting enzyme in the reverse transsulfuration pathway, induces premature senescence in human endothelial cells. We found that CBS depletion induces mild mitochondrial dysfunction and increases the sensitivity of endothelial cells to homocysteine, a known inducer of endothelial cell senescence and an established risk factor for vascular disease. Our finding that CBS deficiency induces endothelial cell senescencein vitro, involving both mitochondrial dysfunction and increased susceptibility of the cells to homocysteine, suggests a new mechanism linking CBS deficiency to vascular aging and disease.
