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Biology subjects

Pieterse, L.

Publications and source records attributed to Pieterse, L..

3 recordsLinked to original sources

Encephalitic Alphavirus Infection Induces PARP-1 Hyperactivation Mediated Energy Collapse in Motor Neurons

Motor neurons are highly vulnerable to metabolic stress, yet the mechanisms driving their degeneration during neurotropic alphavirus infections remain unclear. Venezuelan equine encephalitis virus (VEEV) causes motor neuron injury, but the intrinsic pathways underlying this susceptibility are not fully defined. Previous work suggests alphavirus-infected motor neurons may die through caspase-independent mechanisms. Here, we show that VEEV infection induces sustained activation of the DNA repair enzyme poly(ADP-ribose) polymerase-1 (PARP-1), leading to depletion of NAD+ and ATP in murine NSC34 motor neuron-like cells and human iPSC-derived motor neurons. These metabolic changes precede mitochondrial depolarization and cell death. Pharmacological inhibition or genetic reduction of PARP-1 partially restores NAD+ and ATP and improves cell survival, indicating that PARP-1 hyperactivation directly contributes to energetic collapse and intrinsic motor neuron death. These results identify PARP-1 as a key driver of energy failure during VEEV infection and a potential target to limit neuronal injury in neurotropic viral infections.

microbiology↗

SARS-CoV-2 variants from long-term, persistently infected immunocompromised patients have altered syncytia formation, temperature-dependent replication, and serum neutralizing antibody escape

SARS-CoV-2 infection of immunocompromised individuals often leads to prolonged detection of viral RNA and infectious virus in nasal specimens, presumably due to the lack of induction of an appropriate adaptive immune response. Mutations identified in virus sequences obtained from persistently infected patients bear signatures of immune evasion and have some overlap with sequences present in variants of concern. We characterized virus isolates from two COVID-19 patients undergoing immunosuppressive cancer therapy, with all isolates obtained greater than 100 days after the initial COVID-19 diagnoses and compared to an isolate from the start of the infection. Isolates from an individual who never mounted an antibody response specific to SARS-CoV-2 despite the administration of convalescent plasma showed slight reductions in plaque size and some showed temperature-dependent replication attenuation on human nasal epithelial cell culture compared to the virus that initiated infection. An isolate from another patient - who did mount a SARS-CoV-2 IgM response - showed temperature dependent changes in plaque size as well as increased syncytia formation and escape from serum neutralizing antibody. Our results indicate that not all virus isolates from immunocompromised COVID-19 patients display clear signs of phenotypic change, but increased attention should be paid to monitoring virus evolution in this patient population.

microbiology↗

Discovery of populations endemic to a marine biogeographical transition zone

AimBiogeographical transition zones are areas of overlap between the faunas of adjacent biogeographical entities. Particularly, the well-defined transition zones along linear coastlines are interesting natural laboratories to study dispersal and incipient speciation. Few studies have explored whether marine biogeographical transition zones harbour biodiversity that is distinct from that of the biogeographical entities they separate. The Wild Coast in eastern South Africa is a poorly-studied transition zone between regions warm-temperate and subtropical faunas, and is generally considered to be an area of faunal overlap. LocationThe South African portion of the Western Indian Ocean MethodsSequences of the DNA barcoding marker COI were generated from 306 estuarine sandprawns (Callichirus kraussi) collected at 13 sites. Genetic structure and evolutionary history were assessed using a haplotype network and a Bayesian discrete phylogeographic analysis. ResultTwo populations were identified whose ranges are centred on the Wild Coast, a rare one in the northern portion and a more common one in the central and southern portion of this biogeographical transition zone. These populations are not closely related to each other, but descend from subtropical and warm-temperate sister populations, respectively. ConclusionsThis is the first study to indicate that the Wild Coast marine biogeographical transition zone is not merely an area of faunal overlap, and one of very few studies to have discovered genetically unique populations within a marine biogeographical transition zone. The Wild Coast may harbour additional unique biodiversity that remains to be discovered, including rare species that require protection. More research is required to understand how this environmentally dynamic marine biogeographical transition zone differs from the adjacent biogeographical provinces.

ecology↗