@Nucleocapsoid @HNimanFC @mrmickme2 @0bFuSc8 @PeacockFlu @CVRHutchinson @SCOTTeHENSLEY To add to thread linked above, human British Columbia H5 case has a HA sequence (GISAID EPI_ISL_19548836) that is ambiguous at *both* site Q226 and site E190 (H3 numbering)
Both these sites play an important role in sialic acid binding specificity
@Nucleocapsoid @HNimanFC @mrmickme2 @0bFuSc8 @PeacockFlu @CVRHutchinson @SCOTTeHENSLEY If you are searching literature, these sites are E190 and Q226 in H3 numbering, E186 and Q222 in mature H5 numbering, and E202 and Q238 in sequential H5 numbering (see: )dms-vep.org/Flu_H5_America…
@Nucleocapsoid @HNimanFC @mrmickme2 @0bFuSc8 @PeacockFlu @CVRHutchinson @SCOTTeHENSLEY Ambiguous codons are "ga[gt]" and "ca[at]"
The possible amino under these codes are E or D at 190, and G or H at 226
It would be great to examine deep sequencing data at these sites
Thanks to British Columbia CDC & Canada Public Health for sharing consensus sequences already
@Nucleocapsoid @HNimanFC @mrmickme2 @0bFuSc8 @PeacockFlu @CVRHutchinson @SCOTTeHENSLEY So sorry, that should read *Q* or H at 226 (for "ca[at]")
@Nucleocapsoid @HNimanFC @mrmickme2 @0bFuSc8 @PeacockFlu @CVRHutchinson @SCOTTeHENSLEY Below are HA mutations relative to two major candidate vaccine viruses
Several are in antigenic regions. However, our deep mutational scanning (dms-vep.org/Flu_H5_America…) suggest none of these mutations have a dramatic antigenic effect re neutralization by mouse or ferret sera
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Here is analysis of HA mutations in H5 influenza case in Missouri resident without known contact w animals or raw milk.
TLDR: there is one HA mutation that strongly affects antigenicity, and another that merits some further study.
As background, CDC recently released partial sequence of A/Missouri/121/2024, which is virus from person in Missouri who was infected with H5 influenza.
Here I am analyzing HA protein from this release, GISAID accession EPI_ISL_19413343cdc.gov/bird-flu/spotl…
Sequence covers all of HA except signal peptide, and residues 325-351 (sequential numbering) / 312-335 (H3 numbering). The missing residues encompass HA1-HA2 boundary, and any missed mutations there unlikely to affect antigenicity or receptor binding, but could affect stability.
In new study led by @bblarsen1 in collab w @veeslerlab @VUMC_Vaccines we map functional & antigenic landscape of Nipah virus receptor binding protein (RBP)
Results elucidate constraints on RBP function & provide insight re protein’s evolutionary potentialbiorxiv.org/content/10.110…
Nipah is bat virus that sporadically infects humans w high (~70%) fatality rate. Has been limited human transmission
Like other paramyxoviruses, Nipah uses two proteins to enter cells: RBP binds receptor & then triggers fusion (F) protein by process that is not fully understood
RBP forms tetramer in which 4 constituent monomers (which are all identical in sequence) adopt 3 distinct conformations
RBP binds to two receptors, EFNB2 & EFNB3
RBP’s affinity for EFNB2 is very high (~0.1 nM, over an order of magnitude higher than SARSCoV2’s affinity for ACE2)
Over 4 yrs after being first to publicly release SARS-CoV-2 genome, Yong-Zhen Zhang just published large set of viral seqs from first stage of COVID-19 outbreak in China
Zhang recruited nearly all COVID-19 patients hospitalized at Shanghai Public Health Center in first 2/3 (Jan-Sep) of 2020.
The largest source of Shanghai patients in Jan/Feb 2020 was imported cases from Wuhan or elsewhere in Hubei, thereby providing window into Wuhan outbreak.
Overall, Zhang obtained 343 near-full-length SARS-CoV-2 sequences from 226 distinct patients, including 133 sequences from samples collected no later than Feb-15-2020.
A phylogenetic tree showing these sequences is below.
In new study led by Caleb Carr & @khdcrawford, we measure how all mutation to Lassa virus glycoprotein complex (GPC) affect cell entry & antibody escape
Results show how prospective assessment of effects of mutations can inform design of countermeasures biorxiv.org/content/10.110…
As background, Lassa virus causes of thousands of deaths each year, mostly from spillovers from its rodent host, but there is occasional human-to-human transmission.
Lassa is biosafety-level-4 priority pathogen, & efforts are underway to develop vaccines & antibody therapeutics.
We used pseudovirus deep mutational scanning to study effects of nearly all 9,820 amino-acid mutations to Lassa’s GPC at biosafety-level-2 by making genotype-phenotype linked libraries of lentiviral pseudotypes blog.addgene.org/viral-vectors-…