Advent of next generation sequencing (NGS) techniques has allowed identification of theses intra-individual viral subpopulations, called quasispecies, in patients infected with SARS-CoV 11 and MERS-CoV 12, suggesting their existence for SARS-CoV-2 yet 7 with an estimated average genetic distance of ~ 8.36 × 10 –4. It may suggest, however, that the origin of these new inter-individual viral entities called "variants" is more subtle as several teams have, in an analogous way to HIV or other RNA viruses, studied the possibility of the existence of significant intra-individual variability leading to this genetic polymorphism 10. As an example, a link between increased mutations and treatment has recently been demonstrated, as well as the selection pressure of the host immune system, associated with more mutations in spike domain 9. Thus, new mutants, clones, and then viral variants born from each infected host, having different infectivity and contagiousness and playing in an incredible way on the evolution of the different epidemic currents of COVID-19 8. The rate of evolution of SARS-CoV-2 is considered moderate, estimated at 1.19–1.31 × 10 3 substitutions per site per year 6, which tends to increase today to around 2.68–3.86 × 10 3 per site per year, mainly due to the low fidelity of its RdRp, which could evolve with time 7. Like other RNA viruses, beta-coronaviruses can have complex and dynamic cycles of genomic variation within a population or within a single host, and thus exhibit significant polymorphism 6. Phylogenetic analysis of coronavirus genomes has revealed that SARS-CoV-2 belongs to subgenus Sarbecovirus in genus Betacoronavirus, with high similarity (96%) to bat betacoronavirus RaTG13, suggesting its potential zoonotic origin 5. SARS-CoV-2 was sequenced as an enveloped ssRNA virus with a complete genomic sequence containing 29,903 nucleotides and encoding 7986 amino acids 4. In December 2019, a new coronavirus, severe acute respiratory syndrome-Coronavirus-2 (SARS-CoV-2), was reported for the first time in the city of Wuhan, Hubei Province, China, causing a rapidly pandemic severe infection in humans (COVID 19). They belong to the order Nidovirales, family Coronaviridae, subfamily Coronavirinae, and cause zoonotic infections in many vertebrates 3. Among them, coronaviruses are the largest group of non-segmented, single-stranded, positive-sense ribonucleic acid viruses (+ ssRNA) 2. The question of the SARS-CoV-2 viral variants’ genesis remains to be further investigated, with the need to prevent new viral propagations and their consequences, and quasi-species analysis could be an important key to watch out.Īcute infectious respiratory diseases is one of the main causes of morbidity and mortality worldwide, and viral infections of lower respiratory tract account for a large proportion 1. Furthermore, we found minority N501Y and P681H mutation clouds in all patients, with no significant differences found both groups. In the detailed analysis, we found a greater difference between persistent and non-persistent patients with non-severe COVID 19, and between the two groups infected with clade 20A. Global intra-individual variability in persistent patients was found to be higher than in controls (mean 5.3%, Standard deviation 0.9 versus 4.6% SD 0.3, respectively, p < 0.001). We performed a prospective high-throughput sequencing study (ARTIC Nanopore) of SARS-CoV-2 from so-called "persistent" patients, comparing them with a non-persistent population, and analyzing the quasi-species present in a single sample at time t. The nasopharyngeal persistence of infectious virus beyond 17 days proves its constant interaction with the human immune system and increases the intra-individual mutational possibilities. At the time of a new and unprecedented viral pandemic, many questions are being asked about the genomic evolution of SARS-CoV-2 and the emergence of different variants, leading to therapeutic and immune evasion and survival of this genetically highly labile RNA virus.
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