Dataset Information

A Novel and Expanding SARS-CoV-2 Variant, B.1.526, Identified in New York.

ABSTRACT: Recent months have seen surges of SARS-CoV-2 infection across the globe along with considerable viral evolution^1-3. Extensive mutations in the spike protein may threaten efficacy of vaccines and therapeutic monoclonal antibodies⁴. Two signature mutations of concern are E484K, which plays a crucial role in the loss of neutralizing activity of antibodies, and N501Y, a driver of rapid worldwide transmission of the B.1.1.7 lineage. Here, we report the emergence of a novel variant lineage B.1.526 that contains E484K and its alarming rise to dominance in New York City in recent months. This variant is partially or completely resistant to two therapeutic monoclonal antibodies in clinical use. It is also less susceptible to neutralization by convalescent plasma or vaccinee sera, posing a modest antigenic challenge. The B.1.526 lineage has now been reported from all 50 states in the US and numerous other countries. B.1.526 has rapidly replaced non-variant lineages in New York, with an estimated transmission advantage of 35%. Although B.1.526 initially outpaced B.1.1.7 in the region, its growth has slowed concurrent with the rise of B.1.1.7. In states surrounding New York, B.1.526 continues to increase where B.1.1.7 has not yet reached dominance, persistently replacing non-variant lineages. Such transmission dynamics, together with the relative antibody resistance of its E484K sub-lineage, would warrant consideration of B.1.526 as a SARS-CoV-2 variant of concern.

SUBMITTER: Annavajhala MK

PROVIDER: S-EPMC7924303 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Emergence and Expansion of the SARS-CoV-2 Variant B.1.526 Identified in New York.

Annavajhala Medini K MK Mohri Hiroshi H Wang Pengfei P Nair Manoj M Zucker Jason E JE Sheng Zizhang Z Gomez-Simmonds Angela A Kelley Anne L AL Tagliavia Maya M Huang Yaoxing Y Bedford Trevor T Ho David D DD Uhlemann Anne-Catrin AC

medRxiv : the preprint server for health sciences 20210804

Recent months have seen surges of SARS-CoV-2 infection across the globe with considerable viral evolution<sup>1-3</sup>. Extensive mutations in the spike protein may threaten efficacy of vaccines and therapeutic monoclonal antibodies<sup>4</sup>. Two signature mutations of concern are E484K, which plays a crucial role in the loss of neutralizing activity of antibodies, and N501Y, a driver of rapid worldwide transmission of the B.1.1.7 lineage. Here, we report the emergence of variant lineage B.1 ...[more]

PMID: 33655278

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Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that was first reported in Wuhan, China in December of 2019 and has since caused a global pandemic resulting in millions of deaths and tens of millions of patients testing positive for infection. Analysis of different viral strains has identified a D614G change in the spike protein that is correlated with the virus becoming more transmissible. While studies have shown G614 viruses to be more transmissible, the effects of this mutation on the host response, especially on the cellular level, are yet to be fully elucidated. In this experiment we infected NHBE cells with the Washington (D614) strain or the New York (G614) strains of SARS-CoV-2. We generated RNA sequencing data at three different time points to improve our understanding of how the intracellular host response differs between infections with these two strains. We analyzed these data with a bioinformatics pipeline that identifies differentially expressed genes, enriched Gene Ontology terms and dysregulated signaling pathways. We detected over 2,000 differentially expressed genes, over 600 Gene Ontology terms, and 29 affected pathways between the two treatments. Many of these entities play a role in immune signaling and response. When comparing the different strains and different time points we found more overall similarities between matched time points than across different time points with the same strain. When specifically comparing the affected pathways, we saw that the 24hr time point of the New York strain was more similar to the 12hr time point of the Washington strain with a large number of pathways related to translation being inhibited in both strains at these time points. These results suggest that D614G substitution in the spike protein, combined with other nonsynonymous changes in the viral gene products cause distinct responses in infected host cells, especially relating to how quickly translation is dysregulated after infection. These observed differences in the intracellular host response to infection could play a role in driving the increase in pathogenicity and mortality seen in the New York outbreaks versus the Washington outbreaks at the beginning of the SARS-CoV-2 pandemic.

Dataset Information

A Novel and Expanding SARS-CoV-2 Variant, B.1.526, Identified in New York.

Publications

Emergence and Expansion of the SARS-CoV-2 Variant B.1.526 Identified in New York.

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