RESUMEN
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a positive-sense, single-stranded RNA genome-containing virus which has infected millions of people all over the world. The virus has been mutating rapidly enough, resulting in the emergence of new variants and sub-variants which have reportedly been spread from Wuhan city in China, the epicenter of the virus, to the rest of China and all over the world. The occurrence of mutations in the viral genome, especially in the viral spike protein region, has resulted in the evolution of multiple variants and sub-variants which gives the virus the benefit of host immune evasion and thus renders modern-day vaccines and therapeutics ineffective. Therefore, there is a continuous need to study the genetic characteristics and evolutionary dynamics of the SARS-CoV-2 variants. Hence, in this study, a total of 832 complete genomes of SARS-CoV-2 variants from the cities of Taiyuan and Wuhan in China was genetically characterized and their phylogenetic and evolutionary dynamics studied using phylogenetics, genetic similarity, and phylogenetic network analyses. This study shows that the four most prevalent lineages in Taiyuan and Wuhan are as follows: the Omicron lineages EG.5.1.1, followed by HK.3, FY.3, and XBB.1.16 (Pangolin classification), and clades 23F (EG.5.1), followed by 23H (HK.3), 22F (XBB), and 23D (XBB.1.9) (Nextclade classification), and lineage B followed by the Omicron FY.3, lineage A, and Omicron FL.2.3 (Pangolin classification), and the clades 19A, followed by 22F (XBB), 23F (EG.5.1), and 23H (HK.3) (Nextclade classification), respectively. Furthermore, our genetic similarity analysis show that the SARS-CoV-2 clade 19A-B.4 from Wuhan (name starting with 412981) has the least genetic similarity of about 95.5% in the spike region of the genome as compared to the query sequence of Omicron XBB.2.3.2 from Taiyuan (name starting with 18495234), followed by the Omicron FR.1.4 from Taiyuan (name starting with 18495199) with ~97.2% similarity and Omicron DY.3 (name starting with 17485740) with ~97.9% similarity. The rest of the variants showed ≥98% similarity with the query sequence of Omicron XBB.2.3.2 from Taiyuan (name starting with 18495234). In addition, our recombination analysis results show that the SARS-CoV-2 variants have three statistically significant recombinant events which could have possibly resulted in the emergence of Omicron XBB.1.16 (recombination event 3), FY.3 (recombination event 5), and FL.2.4 (recombination event 7), suggesting some very important information regarding viral evolution. Also, our phylogenetic tree and network analyses show that there are a total of 14 clusters and more than 10,000 mutations which may have probably resulted in the emergence of cluster-I, followed by 47 mutations resulting in the emergence of cluster-II and so on. The clustering of the viral variants of both cities reveals significant information regarding the phylodynamics of the virus among them. The results of our temporal phylogenetic analysis suggest that the variants of Taiyuan have likely emerged as independent variants separate from the variants of Wuhan. This study, to the best of our knowledge, is the first ever genetic comparative study between Taiyuan and Wuhan cities in China. This study will help us better understand the virus and cope with the emergence and spread of new variants at a local as well as an international level, and keep the public health authorities informed for them to make better decisions in designing new viral vaccines and therapeutics. It will also help the outbreak investigators to better examine any future outbreak.
Asunto(s)
COVID-19 , Evolución Molecular , Genoma Viral , Mutación , Filogenia , SARS-CoV-2 , SARS-CoV-2/genética , SARS-CoV-2/clasificación , China/epidemiología , Humanos , COVID-19/virología , COVID-19/epidemiología , Glicoproteína de la Espiga del Coronavirus/genética , Ciudades , Betacoronavirus/genética , Betacoronavirus/clasificaciónRESUMEN
The beak and feather disease virus (BFDV), causative agent of Psittacine beak and feather disease (PBFD), is a highly fatal and widespread virus that infects both the wild and captive Psittaciformes around the world. The BFDV genome is a ssDNA of approximately 2 kb in size, making it among the smallest known pathogenic viruses. Though, the virus is placed in Circoviridae family of the Circovirus genus, there is no classification system on clade and sub-clade level according to the International Committee on Taxonomy of Viruses and the strains are grouped on the bases of geographic locations. Thus, we provide the latest and robust phylogenetic classification of BFDVs in this study based on full-length genomic sequences, grouping all the available 454 strains detected during 1996-2022 into two distinct clades, e.g., GI and GII. The GI clade is further divided into six sub-clades (GI a-f), while GII into two sub-clades (GII a and b). In addition, the phylogeographic network identified high variability among the BFDV strains, showing several branches, where all the branches are connected to four strains, e.g., BFDV-ZA-PGM-70A(GenBank ID: HM748921.1, 2008-South Africa), BFDV-ZA-PGM-81A(GenBank ID: JX221009.1, 2008-South Africa), BFDV14(GenBank ID: GU015021.1, 2010-Thailand) and BFDV-isolate-9IT11(GenBank ID: KF723390.1, 2014-Italy). Furthermore, we identified 27 recombination events in the rep (replication-associated protein) and cap (capsid protein) coding regions using the complete genomes of BFDVs. Similarly, the amino acids variability analysis indicated that both the rep and cap regions are highly variable with values exceeding the variability coefficient estimation limit of 1.00, speculating the possible amino acids drift with the emergence of new strains. The findings provided in this study may offer the latest phylogenetic, phylogeographic and evolutionary landscape of the BFDVs.
Asunto(s)
Circovirus , Filogenia , Filogeografía , Circovirus/genética , Genoma Viral , Genotipo , Proteínas Virales/genéticaRESUMEN
The cGAS-cGAMP-STING pathway is an important innate immune signaling cascade responsible for the sensing of abnormal cytosolic double-stranded DNA (dsDNA), which is a hallmark of infection or cancers. Recently, tremendous progress has been made in the understanding of the STING activation mechanism from various aspects. In this review, the molecular mechanism of activation of STING protein based on its structural features is briefly discussed. The underlying molecular mechanism of STING activation will enable us to develop novel therapeutics to treat STING-associated diseases and understand how STING has evolved to eliminate infection and maintain immune homeostasis in innate immunity.