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Resistance mutations that distinguish HIV-1 envelopes with discordant VRC01 phenotypes from multi-lineage infections in the HVTN703/HPTN081 trial: implications for cross-resistance.
J Virol
January 2025
SA MRC Antibody Immunity Research Unit, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Parktown, Johannesburg, South Africa.
The Antibody Mediated Prevention (AMP) trials showed that passively infused VRC01, a broadly neutralizing antibody (bNAb) targeting the CD4 binding site (CD4bs) on the HIV-1 envelope protein (Env), protected against neutralization-sensitive viruses. We identified six individuals from the VRC01 treatment arm with multi-lineage breakthrough HIV-1 infections from HVTN703, where one variant was sensitive to VRC01 (IC < 25 ug/mL) but another was resistant. By comparing Env sequences of resistant and sensitive clones from each participant, we identified sites predicted to affect VRC01 neutralization and assessed the effect of their reversion in the VRC01-resistant clone on neutralization sensitivity.
View Article and Find Full Text PDFEvolution and divergence of the role of plant ethylene receptor-related histidine kinases in abscisic acid signaling.
Biochem Biophys Res Commun
January 2025
Department of Bioscience, Tokyo University of Agriculture, Tokyo, 156-8502, Japan. Electronic address:
Plant responses to the water environment are mediated by ethylene (submergence response) and abscisic acid (ABA, drought response). Ethylene is perceived by a family of histidine kinase receptors (ETR-HKs), which regulate the activity of the downstream B3 Raf-like (RAF) kinase CONSTITUTIVE TRIPLE RESPONSE1 (CTR1) in an ethylene-dependent manner. We previously demonstrated in the moss Physcomitrium patens that SNF1-related protein kinase 2 (SnRK2), an essential kinase in osmostress responses in land plants, is activated by the B3-RAF kinase ARK, which is also regulated by ETR-HKs in an ABA- and osmostress-dependent manner.
View Article and Find Full Text PDFModifications to rhesus macaque TCR constant regions improve TCR cell surface expression.
PLoS One
January 2025
AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America.
T cell immunotherapy success is dependent on effective levels of antigen receptor expressed at the surface of engineered cells. Efforts to optimize surface expression in T cell receptor (TCR)-based therapeutic approaches include optimization of cellular engineering methods and coding sequences, and reducing the likelihood of exogenous TCR α and β chains mispairing with the endogenous TCR chains. Approaches to promote correct human TCR chain pairing include constant region mutations to create an additional disulfide bond between the two chains, full murinization of the constant region of the TCR α and β sequences, and a minimal set of murine mutations to the TCR α and β constant regions.
View Article and Find Full Text PDFUnveiling the unusual i-motif-derived architecture of a DNA aptamer exhibiting high affinity for influenza A virus.
Nucleic Acids Res
January 2025
Chemistry Department, Lomonosov Moscow State University, Moscow 119991, Russia.
Non-canonical nucleic acid structures play significant roles in cellular processes through selective interactions with proteins. While both natural and artificial G-quadruplexes have been extensively studied, the functions of i-motifs remain less understood. This study investigates the artificial aptamer BV42, which binds strongly to influenza A virus hemagglutinin and unexpectedly retains its i-motif structure even at neutral pH.
View Article and Find Full Text PDFAn intron-split microRNA mediates cleavage of the mRNA encoded by low phosphate root in Solanaceae.
Planta
January 2025
School of Biological Sciences, University of East Anglia, Norwich Research Park, Norwich, UK.
A microRNA with a non-canonical precursor structure harbours an intron in between its miRNA-5p and miRNA-3p relevant for its biogenesis, is conserved across Solanaceae, and targets the mRNA of low phosphate root. Hundreds of miRNAs have been identified in plants and great advances have been accomplished in the understanding of plant miRNA biogenesis, mechanisms and functions. Still, many miRNAs, particularly those with less conventional features, remain to be discovered.
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