Biology subjects

Brown, J. C.

Publications and source records attributed to Brown, J. C..

3 recordsLinked to original sources

bioRxiv2021

Increased transmission of SARS-CoV-2 lineage B.1.1.7 (VOC 2020212/01) is not accounted for by a replicative advantage in primary airway cells or antibody escape

Lineage B.1.1.7 (Variant of Concern 202012/01) is a new SARS-CoV-2 variant which was first sequenced in the UK in September 2020 before becoming the majority strain in the UK and spreading worldwide. The rapid spread of the B.1.1.7 variant results from increased transmissibility but the virological characteristics which underpin this advantage over other circulating strains remain unknown. Here, we demonstrate that there is no difference in viral replication between B.1.1.7 and other contemporaneous SARS-CoV-2 strains in primary human airway epithelial (HAE) cells. However, B.1.1.7 replication is disadvantaged in Vero cells potentially due to increased furin-mediated cleavage of its spike protein as a result of a P681H mutation directly adjacent to the S1/S2 cleavage site. In addition, we show that B.1.1.7 does not escape neutralisation by convalescent or post-vaccination sera. Thus, increased transmission of B.1.1.7 is not caused by increased replication, as measured on HAE cells, or escape from serological immunity.

microbiology↗

bioRxiv2020

The furin cleavage site of SARS-CoV-2 spike protein is a key determinant for transmission due to enhanced replication in airway cells.

SARS-CoV-2 enters cells via its spike glycoprotein which must be cleaved sequentially at the S1/S2, then the S2 cleavage sites (CS) to mediate membrane fusion. SARS-CoV-2 has a unique polybasic insertion at the S1/S2 CS, which we demonstrate can be cleaved by furin. Using lentiviral pseudotypes and a cell-culture adapted SARS-CoV-2 virus with a S1/S2 deletion, we show that the polybasic insertion is selected for in lung cells and primary human airway epithelial cultures but selected against in Vero E6, a cell line used for passaging SARS-CoV-2. We find this selective advantage depends on expression of the cell surface protease, TMPRSS2, that allows virus entry independent of endosomes thus avoiding antiviral IFITM proteins. SARS-CoV-2 virus lacking the S1/S2 furin CS was shed to lower titres from infected ferrets and was not transmitted to cohoused sentinel animals. Thus, the polybasic CS is a key determinant for efficient SARS-CoV-2 transmission.

microbiology↗

bioRxiv2020

Role of gene length in control of human gene expression; chromosome-specific and tissue-specific effects

BackgroundThis study was carried out to pursue the observation that the level of gene expression is affected by gene length in the genomes of higher vertebrates. As transcription is a time-dependent process, it is expected that gene expression will be inversely related to gene length, and this is found to be the case. Here I describe the results of studies performed with the human genome to test whether the gene length/gene expression linkage is affected by two factors, the chromosome where the gene is located and the tissue where it is expressed. Experimental designStudies were carried out with a database of 2413 human genes that were divided into short, mid-length and long groups. Each of the 24 human chromosomes was then characterized according to the proportion of each gene length group present. A similar analysis was performed with 19 human tissues. The proportion of short, mid-length and long genes was noted for each tissue. ResultsBoth chromosome and tissue studies revealed new information about the role of gene length in control of gene expression. Chromosome studies led to the identification of two chromosome populations that differ in the level of short gene expression. Tissue studies support the conclusion that short, highly expressed genes are enriched in tissues that produce protein products that are exported from the host cell.

immunology↗