Biology subjects

Kibria, M. G.

Publications and source records attributed to Kibria, M. G..

6 recordsLinked to original sources

bioRxiv2026

Intermediate, rather than Isohydric or Anisohydric, Species were More Resilient to an Extreme Heatwave in a Common Garden in Sydney

Urban forests are increasingly exposed to climate extremes, yet selecting resilient urban species remains difficult as it is unclear why some species fail and others succeed. We monitored growth and survival of 48 urban tree and shrub species, respectively, for about five years after planting, plus we quantified species' crown dieback after a natural extreme heatwave (three days with temperatures exceeding 40 degrees C) in a common garden in Sydney, Australia. For 30 species we measured 15 plant functional traits, including both hydraulic and morphological traits. Native species had less crown dieback and higher absolute growth but lower survival than exotic species. Plant functional traits linked to heat and drought tolerance explained 20-30% of the variation in observed crown dieback across species. Extensive dieback exceeding 40% after the extreme heatwave was found for seven species with large leaf size (and leaf width), high leaf relative water content, and low wood density. Nonlinear relationships between crown dieback and leaf water potential traits identified that both isohydric and anisohydric species were vulnerable, indicating that vulnerability did not align neatly with a single hydraulic strategy. Hydraulic failure likely occurred for some, but not all, vulnerable isohydric and anisohydric species, suggesting vulnerability of certain species was directly caused by cumulative thermal stress. Importantly, survival was not related to any single functional trait, indicating that crown dieback was a more sensitive and earlier indicator of cumulative thermal stress than mortality. These findings support a shift from climate of origin-based to trait-based species selection in urban forestry.

physiology↗

bioRxiv2026

Structure and antigenicity of the 2026 Bundibugyo virus glycoprotein

An outbreak of ebolavirus disease caused by a new zoonotic spillover of Bundibugyo virus (BDBV) is currently spreading at an unprecedented pace in the Democratic Republic of the Congo and Uganda. The outbreak has resulted in 7,733 cases with a case-fatality ratio of 48%, yet no BDBV-specific vaccines or therapeutics are available. The ebolavirus glycoprotein (GP) promotes viral entry and is the target of neutralizing antibodies and vaccine development. Here, we engineered a soluble, prefusion-stabilized GP trimer from a contemporary BDBV isolate and determined its cryo-electron microscopy structure bound to the broadly neutralizing antibody EBOV-515. It reveals the molecular basis for EBOV-515 cross-reactivity and suggests that the antibody inhibits viral entry by interfering with NPC1 engagement in addition to trapping GP in the prefusion conformation and hindering glycan cap cleavage. Mapping lineage-defining substitutions identified changes in GP1 and GP2, including R506S within an antigenic site targeted by multiple broadly neutralizing antibodies recognizing the fusion loop. Nevertheless, we found that several glycan cap-, GP base-, and HR2-directed antibodies cross-reacted and neutralized BDBV DRC/2026 GP pseudovirus with potency comparable or greater to that observed against earlier BDBV isolates and the Zaire ebolavirus Makona/2024 isolate. These findings define the antigenic properties of contemporary BDBV GP and delineate conserved epitopes as ideal targets for antibody therapeutics and for the development of pan-ebolavirus vaccines.

biochemistry↗

bioRxiv2025

Affinity Maturation and Light-Chain-Mediated Paratope Diversification Anticipate Viral Evolution

A key goal of vaccinology is to train the immune system to combat current pathogens while simultaneously preparing it for future evolved variants. Understanding factors contributing to anticipatory breadth, wherein affinity maturation against an ancestral strain yields neutralization capacity against evolved variants, is therefore of great importance. Here, we investigated the mechanism of anticipatory breadth development in a public antibody family targeting the functionally restricted ACE2 binding site on SARS-CoV-2. IGHV3-53/66 antibodies isolated from memory B cells of infection-naive individuals vaccinated with the ancestral Wuhan-strain mRNA vaccine frequently neutralized evolved Omicron variants and contained several hallmark mutations previously shown to enhance neutralization breadth. Comparative analyses with antibodies from Omicron breakthrough infections revealed that breadth-associated patterns of somatic hypermutation emerged independently of variant exposure. However, Omicron infection had a marked impact on light chain pairing frequencies, suggestive of variant-imposed selection of favorable light chains. Analysis of available IGHV3-53/66 antibody structures complexed with SARS-CoV-2 receptor binding domain (RBD) clarified these findings; convergent somatic mutations on the heavy chain largely refined contacts with invariant RBD residues, while light chain pairings shifted epitopes to avoid steric challenges posed by Omicron mutations. These findings support a model of anticipatory breadth with three key elements: (1) targeting of a functionally restricted epitope, (2) affinity maturation to establish an affinity buffer, and (3) variable chain pairing to generate paratope diversity. These elements each serve to compensate for a distinct consequence of viral mutagenesis, offering a mechanistic framework for anticipating viral evolution. Graphical Summary O_FIG O_LINKSMALLFIG WIDTH=157 HEIGHT=200 SRC="FIGDIR/small/672735v1_ufig1.gif" ALT="Figure 1"> View larger version (51K): org.highwire.dtl.DTLVardef@1e4e893org.highwire.dtl.DTLVardef@1610bddorg.highwire.dtl.DTLVardef@520909org.highwire.dtl.DTLVardef@1cf4edc_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2025

Effect of the S2' site cleavage on SARS-CoV-2 spike

SARS-CoV-2 initiates infection of host cells by fusing its envelope lipid bilayer with the cell membrane. To overcome kinetic barriers for membrane fusion, the virus-encoded spike (S) protein refolds from a metastable prefusion state to a lower energy, stable postfusion conformation. The protein is first split into S1 and S2 fragments at a proteolytic site after synthesis, and presumably further cleaved at a second site, known as the S2 site, before membrane fusion can occur. We report here a cryo-EM structure of S2 fragment after the S2 cleavage, possibly representing a late fusion intermediate conformation, in which the fusion peptide and transmembrane segment have yet to pack together, distinct from the final, postfusion state. Functional assays demonstrate that the S2 cleavage accelerates membrane fusion, probably by stabilizing fusion intermediates. These results advance our understanding of SARS-CoV-2 entry and may guide intervention strategies against pathogenetic coronaviruses.

biochemistry↗

bioRxiv2023

Antibody-mediated cell entry of SARS-CoV-2

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters host cells by first engaging its cellular receptor angiotensin converting enzyme 2 (ACE2) to induce conformational changes in the virus-encoded spike protein and fusion between the viral and target cell membranes. We report here that certain monoclonal neutralizing antibodies against distinct epitopic regions of the receptor-binding domain of the spike can replace ACE2 to serve as a receptor and efficiently support membrane fusion and viral infectivity. These receptor-like antibodies can function in the form of a complex of their soluble immunoglobulin G with Fc-gamma receptor I, a chimera of their antigen-binding fragment with the transmembrane domain of ACE2 or a membrane-bound B cell receptor, indicating that ACE2 and its specific interactions with the spike protein are dispensable for SARS-CoV-2 entry. These results suggest that antibody responses against SARS-CoV-2 may expand the viral tropism to otherwise nonpermissive cell types; they have important implications for viral transmission and pathogenesis.

microbiology↗

bioRxiv2020

A systematic mutational analysis identifies a 5-residue proline tag that enhances the in vivo immunogenicity of a non-immunogenic model protein 240 folds

Small proteins are generally non-immunogenic, which can be a major hurdle in developing protein and peptide vaccines or producing antibodies for biopharmaceutical usage. For improving a proteins immunogenicity, we previously proposed to use short Solubility Controlling Peptide (SCP) tags that oligomerize proteins into soluble aggregates. Here, we systematically analyzed the effect of SCP-tags that do not induce oligomerization on the immunogenicity of a small, non-immunogenic, model protein, Bovine Pancreatic Trypsin Inhibitor (BPTI-19A; 6 kDa). We assessed the effect of the following ten SCP-tags: Six tags made of five consecutive Arg, Lys, His, Asp, Asn, Pro; one made of seven Pro; two tags made of consecutive Arg-lle and Asn-Ile, all attached at the C-terminus of BPTI-19A; and a 5-proline tag attached at the N-terminus. Circular dichroism, fluorescence, dynamic light scattering measurements, and analytical ultra-centrifugation indicated that the addition of the SCP-tags did not change the secondary structure content nor the tertiary structures of the protein nor its monomeric state. On the other hand, the C-terminus 5-proline (C5P) tag unexpectedly increased the immunogenicity (IgG level) of BPTI-19A by up to 240 fold as assessed by ELISA. Additionally, the 5-arginine tag (C5R) increased the titer by up to 73 fold. The titer increase lasted for several weeks, and the effect was cumulative to that of the Freunds adjuvant, which is commonly used to boost a proteins immunogenicity. Altogether, SCP-tags that do not oligomerize proteins substantially increased the immunogenicity of a non-immunogenic protein, suggesting that the 5-proline and the 5-arginine SCP-tags may provide a novel tool for facilitating the production of antibodies or improving the effectiveness of protein-based vaccines.

immunology↗