Gta 5 beta pharma
Because newly emerging variants can potentially change viral infectivity, transmissibility, and pathogenicity, deep monitoring of SARS-CoV-2 strains circulating globally and locally and evaluation of the effects of detected mutations on virological characteristics are urgent and crucial. Strikingly, the emergence of a SARS-CoV-2 variant, B.1.1.298, is likely associated with the outbreak in farmed minks in Denmark ( Koopmans, 2021 WHO, 2020b), and phylogenetic analysis has provided evidence of mink-to-human transmission of SARS-CoV-2 within Danish mink farms ( Oude Munnink et al., 2021). In the case of SARS-CoV-2, various mammals, such as nonhuman primates ( Chandrashekar et al., 2020 Munster et al., 2020 Yu et al., 2020) and carnivores ( Halfmann et al., 2020 Kim et al., 2020 Shi et al., 2020), can become infected ( Damas et al., 2020 Martínez-Hernández et al., 2020 OIE, 2021). Moreover, cross-species viral infection can accelerate the emergence of diverse viruses ([reviewed in Banerjee et al., 2021 and Parrish et al., 2008). At the end of 2020, another lineage, B.1.427/429 (also known as CAL.20C), has been predominant, particularly in California state, USA ( Deng et al., 2021 Zhang et al., 2021). Additionally, since fall of 2020, new SARS-CoV-2 variants such as B.1.1.7 (also known as a variant of concern 202012/01 or 20I/501Y.V1), B.1.351 (also known as 20H/501Y.V2), and P.1 (also known as 501Y.V3) lineages have emerged in the UK, South Africa, and Brazil, respectively, and have rapidly spread worldwide ( CDC, 2020). However, there is no evidence suggesting that the D614G variant is associated with viral pathogenicity or lethality ( Hou et al., 2020 Korber et al., 2020 Plante et al., 2021a). Recent studies have revealed that the D614G mutation increases the binding affinity of SARS-CoV-2 to ACE2, the SARS-CoV-2 receptor ( Ozono et al., 2021 Yurkovetskiy et al., 2020 Zhou et al., 2021) infectivity ( Ozono et al., 2021 Yurkovetskiy et al., 2020 Zhou et al., 2021), fitness ( Hou et al., 2020 Plante et al., 2021a Zhou et al., 2021), and transmissibility in the human population ( Volz et al., 2021) are also enhanced. A well-studied SARS-CoV-2 mutant harbors a D614G substitution in the spike (S) protein. Since an unusual outbreak in Wuhan, Hubei Province, China, in December 2019 ( Wu et al., 2020 Zhou et al., 2020), SARS-CoV-2 has rapidly spread worldwide, and as of May 2021, COVID-19 remains an ongoing pandemic: more than one-hundred million cases of SARS-CoV-2 infection have been reported worldwide, with more than three million people dying of COVID-19 ( WHO, 2020a).Ī variety of SARS-CoV-2 mutants have emerged during the pandemic and some have dominantly spread (reviewed in Plante et al., 2021b). These data suggest that HLA-restricted cellular immunity potentially affects the evolution of viral phenotypes and that a further threat of the SARS-CoV-2 pandemic is escape from cellular immunity.Ĭoronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Notably, the L452R mutation increases spike stability, viral infectivity, viral fusogenicity, and thereby promotes viral replication. These mutations reinforce affinity toward the host entry receptor ACE2. Here, we demonstrate that two recently emerging mutations in the receptor-binding domain of the SARS-CoV-2 spike protein, L452R (in B.1.427/429 and B.1.617) and Y453F (in B.1.1.298), confer escape from HLA-A24-restricted cellular immunity. Although the sensitivity of naturally occurring SARS-CoV-2 variants to humoral immunity has been investigated, sensitivity to human leukocyte antigen (HLA)-restricted cellular immunity remains largely unexplored. These mutations can affect viral properties such as infectivity and immune resistance. Many SARS-CoV-2 variants with naturally acquired mutations have emerged.