Biology subjects

Adu, O. F.

Publications and source records attributed to Adu, O. F..

4 recordsLinked to original sources

bioRxiv2026

The Q226H Mutation in Avian H5N1 Hemagglutinin Mediates a Path towards Structural Adaptation in Humans

The global outbreak of highly pathogenic avian influenza (HPAI) A(H5N1) among birds and the spillover to mammals increases the risk for humans. A recent case in British Columbia with a clade 2.3.4.4b H5 virus infection revealed a mixture of 226Q/H in the receptor-binding site of hemagglutinin. While significant changes in pre-existing immunity by H1 or H3 polyclonal sera are not evident, we show that the Q226H mutation enables binding to human-type a2-6 sialic acid receptors. High-resolution cryo-EM structures provide a basis for the alteration in receptor preference and show that a possible path towards human adaptation also requires a conformational change of the bound a2-6-sialylated glycan. Continued surveillance for additional mutations that could enhance this phenotype is warranted.

immunology↗

bioRxiv2025

Distinct evolutionary patterns of endemic and emerging parvoviruses, and the origin of a new pandemic virus.

Emergence of epidemic viruses in new hosts threatens both human and animal populations, and often involves virus evolution to overcome barriers that normally prevent efficient infection and spread in that host. After transfer the separated viruses will evolve in parallel as they spread within the original and new hosts. Here we examine the details of a virus involved in such a host-jumping event, where we define the natural evolution of feline panleukopenia virus (FPV) over 60 years, clarify the origins of the new pandemic canine parvovirus (CPV) that arose in the 1970s, and compare the separate evolution of those viruses over 47 years in cats or dogs. Several live-attenuated FPV vaccine viruses originated from early 1960s isolates or were a recombinant of an early virus, and many sequences in databases proved to be vaccine-derived. The sequences of wild viruses showed that FPV-like strains evolved at [~]25% the rate seen for CPV in dogs, and the higher rate of CPV evolution was consistent since 1979 when a genetic variant became widespread. The common ancestor of the CPV lineage was related to FPVs from Europe, and contained several unique host-adaptive capsid changes associated with canine transferrin receptor type-1 binding. Although the FPV vaccine strains are around 60 years old, little selection for antigenic variation was observed. The distinct evolutionary patterns of these closely related viruses circulating for decades in different hosts emphasizes the complex evolution associated with viral epidemic emergence and spread in endemic and new hosts. SIGNIFICANCE STATEMENTComparing the evolution of a virus in its reservoir host with that seen in a new host will reveal the special circumstances that allow epidemic emergence. A feline parvovirus (FPV) jumping to dogs in the mid-1970s formed canine parvovirus (CPV), which has circulated world-wide until today. The evolutionary rate of FPV in its original hosts was much lower than that of CPV in dogs, and the mutational patterns seen in the different hosts were also distinct. Early CPV isolates differed from the ancestral FPV clade in several key host range mutations. These results highlight the complex biology associated with epidemic emergence, including host-specific rates of lineage evolution and complex origins of host-adaptive mutations. (113/120)

evolutionary biology↗

bioRxiv2024

Cell binding, uptake and infection of influenza A virus using recombinant antibody-based receptors.

Human and avian influenza A viruses bind to sialic acid (Sia) receptors on cells as their primary receptors, and this results in endocytic uptake of the virus. While the role of Sia on glycoproteins and/or glycolipids for virus entry is crucial, the roles of the carrier proteins are still not well understood. Furthermore, it is still unclear how receptor binding leads to infection, including whether the receptor plays a structural or other roles beyond being a simple tether. To enable the investigation of the receptor binding and cell entry processes in a more controlled manner, we have designed a protein receptor for pandemic H1 influenza A viruses. The engineered receptor possesses the binding domains of an anti-HA antibody prepared as a single chain variable fragment (scFv) fused with the stalk, transmembrane and cytoplasmic sequences of the feline transferrin receptor type-1 (fTfR). When expressed in cells that lack efficient display of Sia due to a knockout of the Slc35A1gene which encodes for the Solute Carrier Family 35 transporter (SLC35A1), the anti-H1 receptor was displayed on the cell surface, bound virus or hemagglutinin proteins, and the virus was efficiently endocytosed into the cells. Infection occurred at similar levels to those seen after Sia reconstitution, and treatment with clathrin-mediated endocytosis (CME) inhibitors significantly reduced viral entry. IMPORTANCE.Influenza A viruses mostly circulate among avian reservoirs, and also can jump hosts to cause epidemics in mammals, including among humans. A key interaction of the viruses is with host cell Sia, which vary in chemical form, in their linkages within the oligosaccharide, and in the attachment to surface glycoproteins or glycolipids with different properties. Here we report a new method for examining the processes of receptor binding and uptake into cells during influenza A virus infection, by use of an engineered HA-binding membrane glycoprotein, where an antibody is used as the binding domain and the transferrin receptor uptake structures mediate efficient entry, which should allow us to test and manipulate the processes of cell binding, entry, and infection.

microbiology↗

bioRxiv2023

Viral capsid, antibody, and receptor interactions: experimental analysis of the antibody escape evolution of canine parvovirus

Canine parvovirus (CPV) is a small non-enveloped single-stranded DNA virus that causes serious diseases in dogs worldwide. The original strain of the virus (CPV-2) emerged in dogs during the late-1970s due to a host range switch of a virus similar to the feline panleukopenia virus (FPV) that infected another host. The virus that emerged in dogs had altered capsid receptor- and antibody-binding sites, with some changes affecting both functions. Further receptor and antibody binding changes arose when the virus became better adapted to dogs or to other hosts. Here, we use in vitro selection and deep sequencing to reveal how two antibodies with known interactions select for escape mutations in CPV. The antibodies bind two distinct epitopes, and one largely overlaps the host receptor binding site. We also engineered antibody variants with altered binding structures. Viruses were passaged with the wild type or mutated antibodies, and their genomes deep sequenced during the selective process. A small number of mutations were detected only within the capsid protein gene during the first few passages of selection, and most sites remained polymorphic or were slow to go to fixation. Mutations arose both within and outside the antibody binding footprints on the capsids, and all avoided the TfR-binding footprint. Many selected mutations matched those that have arisen in the natural evolution of the virus. The patterns observed reveal the mechanisms by which these variants have been selected in nature and provide a better understanding of the interactions between antibody and receptor selections. IMPORTANCEAntibodies protect animals against infection by many different viruses and other pathogens, and we are gaining new information about the epitopes that induce antibody responses against viruses and the structures of the bound antibodies. However, less is known about the processes of antibody selection and antigenic escape and the constraints that apply in this system. Here, we use an in vitro model system and deep genome sequencing to reveal the mutations that arise in the virus genome during selection by each of two monoclonal antibodies or their engineered variants. High-resolution structures of each of the Fab: capsid complexes revealed their binding interactions. The engineered forms of the wild-type antibodies or mutant forms allowed us to examine how changes in antibody structure influence the mutational selection patterns seen in the virus. The results shed light on the processes of antibody binding, neutralization escape, and receptor binding, and likely have parallels for many other viruses.

evolutionary biology↗