Biology subjects

Nelson, R.

Publications and source records attributed to Nelson, R..

22 records · Page 2Linked to original sources

bioRxiv2020

Patterns of within-host genetic diversity in SARS-CoV-2

Monitoring the spread of SARS-CoV-2 and reconstructing transmission chains has become a major public health focus for many governments around the world. The modest mutation rate and rapid transmission of SARS-CoV-2 prevents the reconstruction of transmission chains from consensus genome sequences, but within-host genetic diversity could theoretically help identify close contacts. Here we describe the patterns of within-host diversity in 1,181 SARS-CoV-2 samples sequenced to high depth in duplicate. 95% of samples show within-host mutations at detectable allele frequencies. Analyses of the mutational spectra revealed strong strand asymmetries suggestive of damage or RNA editing of the plus strand, rather than replication errors, dominating the accumulation of mutations during the SARS-CoV-2 pandemic. Within and between host diversity show strong purifying selection, particularly against nonsense mutations. Recurrent within-host mutations, many of which coincide with known phylogenetic homoplasies, display a spectrum and patterns of purifying selection more suggestive of mutational hotspots than recombination or convergent evolution. While allele frequencies suggest that most samples result from infection by a single lineage, we identify multiple putative examples of co-infection. Integrating these results into an epidemiological inference framework, we find that while sharing of within-host variants between samples could help the reconstruction of transmission chains, mutational hotspots and rare cases of superinfection can confound these analyses.

genomics↗

bioRxiv2020

Characterization of neutralizing antibodies from a SARS-CoV-2 infected individual

B cells specific for the SARS-CoV-2 S envelope glycoprotein spike were isolated from a COVID-19-infected subject using a stabilized spike-derived ectodomain (S2P) twenty-one days post-infection. Forty-four S2P-specific monoclonal antibodies were generated, three of which bound to the receptor binding domain (RBD). The antibodies were minimally mutated from germline and were derived from different B cell lineages. Only two antibodies displayed neutralizing activity against SARS-CoV-2 pseudo-virus. The most potent antibody bound the RBD in a manner that prevented binding to the ACE2 receptor, while the other bound outside the RBD. Our study indicates that the majority of antibodies against the viral envelope spike that were generated during the first weeks of COVID-19 infection are non-neutralizing and target epitopes outside the RBD. Antibodies that disrupt the SARS-CoV-2 spike-ACE2 interaction can potently neutralize the virus without undergoing extensive maturation. Such antibodies have potential preventive/therapeutic potential and can serve as templates for vaccine-design. IN BRIEFSARS-CoV-2 infection leads to expansion of diverse B cells clones against the viral spike glycoprotein (S). The antibodies bind S with high affinity despite being minimally mutated. Thus, the development of neutralizing antibody responses by vaccination will require the activation of certain naive B cells without requiring extensive somatic mutation. HighlightsO_LIAnalysis of early B cell response to SARS-CoV-2 spike protein C_LIO_LIMost antibodies target non-neutralizing epitopes C_LIO_LIPotent neutralizing mAb blocks the interaction of the S protein with ACE2 C_LIO_LINeutralizing antibodies are minimally mutated C_LI

immunology↗

bioRxiv2019

Spatial and temporal partitioning and tree preference in California woodland ants

Spatial and temporal partitioning of habitat may facilitate diversity and have important impacts on ant communities. To investigate niche overlap in an ant community in a northern California oak woodland, we observed ant foraging on trees in 4 seasonal surveys, each lasting 2 weeks, in a 9.5-hectare plot over the course of a year. Foraging activity in all 5 observed ant species differed by season, time of day, and/or the genera of trees used. Of the 3 ant species most frequently observed, Camponotus semitestaceus was most active during spring and summer nights, Formica moki was most active during spring and summer days, and Prenolepis imparis was most active during both day and night of fall and winter. All ant species preferred native trees to exotic trees and preferred evergreen trees to deciduous trees. Our results suggest that native evergreen oaks such as Quercus agrifolia, currently threatened by sudden oak death (Phytophthora ramorum), may be important for supporting ant biodiversity.

ecology↗

bioRxiv2019

Mutant huntingtin protein alters the response of microglial cells to inflammatory stimuli

Huntingtons disease (HD) is a progressive neurodegenerative disease that affects the striatum and cerebral cortex. It is caused by a dominant CAG trinucleotide expansion in exon 1 of the HTT gene. Mutant huntingtin protein (mHtt) is expressed in neurons and immune cells. HD patients demonstrate altered blood cytokine profiles and altered responses of peripheral immune cells to inflammatory stimuli. However, the effects of mHtt on microglial immune responses are not fully understood. Herein we discuss the current understanding of how mHtt alters microglial inflammatory responses. Using lentivirus, we expressed the N171 N-terminal fragment of wild-type or mhtt containing 18 and 82 glutamine repeats in cultured EOC-20 microglial cells. We then measured responses to lipopolysaccharide or interleukin-6. Mutant huntingtin-expressing microglial cells produced less interleukin-6 and nitric oxide in response to lipopolysaccharide stimulation than wild-type huntingtin-expressing cells. However, mHtt-expressing microglia stimulated with interleukin-6 produced more nitric oxide than wild-type cells. Mutant huntingtin-expressing cells had higher basal NF-{kappa}B and further elevations of NF-{kappa}B after interleukin-6 but not lipopolysaccharide stimulation. Thus we demonstrate the potential of mHtt to dampen responses to lipopolysaccharide but potentiate responses to interleukin-6. This work adds to the emerging understanding that mHtt alters not only baseline status of cells but may also result in altered immune responses dependent on the nature of the inflammatory stimuli. We also present our perspective that in human HD the extent of inflammation may depend, in part, on altered responses to varied inflammatory stimuli including environmental factors such as infection.

neuroscience↗