Biology subjects

Kendall, L.

Publications and source records attributed to Kendall, L..

4 recordsLinked to original sources

bioRxiv2026

Intratumoural oncolytic HSV-1 reshapes the local and systemic immune landscape through CD8+ T cell reprogramming

Most oncolytic viruses are delivered by intratumoural injection, and local administration can induce regression of both injected and distant tumours in mice and patients. However, the mechanisms by which local viral infection reprograms systemic immunity remain poorly understood. Here we show that intratumoural RP1, an oncolytic HSV-1 encoding GM-CSF and GALV-GP-R-, drives regression of injected and uninjected murine melanoma tumours and prolongs survival. RP1 elicits coordinated CD4 and CD8 T cell infiltration accompanied by local cytokine remodelling, reshaping the immune landscape at both tumour sites. Leveraging the Timer of Cell Kinetics and Activity (Tocky) system and Kaede photoconvertible protein technology, we resolve the temporal dynamics of CD8 T cell responses following local virotherapy and identify two systemically induced, virus-driven CD8 T cell populations distinguished by TCR engagement kinetics: antigen-engaged Timer-positive viral-induced precursors (VIPs) and Timer-negative KLRG1 viral-induced terminal effectors (VITEs). Single-cell transcriptomic and pseudotime analyses reveal divergent differentiation trajectories; VIPs exhibit sustained antigen engagement within the tumour microenvironment (TME), a transcriptional programme associated with self-renewal, and preferential homing to draining lymph nodes. A VIP-associated gene signature correlates with clinical response to RP1 plus PD-1 blockade in the IGNYTE trial of RP1 and nivolumab in PD-1-refractory melanoma and is independently associated with response to immune checkpoint inhibitor (ICI) therapy in melanoma. These findings establish a mechanistic link between local oncolytic virotherapy, systemic CD8 T cell reprogramming, and durable regression of distant lesions in patients.

cancer biology↗

bioRxiv2024

Jamaican fruit bats (Artibeus jamaicensis) competence for Ebola virus but not Marburg virus is driven by intrinsic differences in viral entry and IFN-I signaling antagonism.

Ebola virus (EBOV) and Marburg virus (MARV) are zoonotic filoviruses that cause hemorrhagic fever in humans. Bat species in both Chiropteran suborders host filoviruses, suggesting that bats may have coevolved with this viral family. Correlative data implicate bats as natural EBOV hosts, but neither a full-length genome nor an EBOV isolate has been found in any bats sampled. Here, we modelled filovirus infection in the Jamaican fruit bat (JFB), Artibeus jamaicensis. Bats were inoculated with either EBOV or MARV through a combination of oral, intranasal, and subcutaneous routes. EBOV-infected bats supported systemic virus replication and shed infectious virus orally. In contrast, MARV replicated only transiently and was not shed. In vitro, JFB cells replicate EBOV more efficiently than MARV, and MARV infection induced innate antiviral responses that EBOV efficiently suppressed. Experiments using VSV pseudoparticles or replicating VSV expressing the EBOV or MARV glycoprotein demonstrated an advantage for EBOV entry and replication early, respectively, in JFB cells. Overall, this study describes filovirus species-specific phenotypes for both JFB and their cells.

immunology↗

bioRxiv2023

Ca2+-sensing receptor regulates neuronal excitability via Kv7 channel and Gi/o protein signalling

Neuropathic pain, a debilitating condition with unmet medical needs, can be charactarised as hyperexcitability of nociceptive neurons caused by dysfunction of ion channels. Voltage-gated potassium channel type 7 (Kv7), responsible for maintaining neuronal resting membrane potential and thus neuronal exitability, resides under tight control of G protein-coupled receptors (GPCR). Calcium-sensing receptor (CaSR) is a GPCR that is known to regulate activity of numerous ion channels, but whether CaSR could control Kv7 channel function has been unexplored until now. Our results demonstrate that CaSR is expressed in recombinant cell models, human induced pluripotent stem cell (hiPSC)-derived nociceptive-like neurons and mouse dorsal root ganglia neurons, and its activation induced depolarisation via Kv7.2/7.3 channel inhibition. The CaSR-Kv7.2/7.3 channel crosslink was mediated via the Gi/o protein/adenylate cyclase/cyclic adenosine monophosphate/protein kinase A signalling cascade. Suppression of CaSR function rescued hiPSC-derived nociceptive-like neurons from algogenic cocktail-induced hyperexcitability. To conclude, this study demonstrates that CaSR-Kv7.2/7.3 channel crosslink via the Gi/o protein signalling pathway effectively regulates neuronal excitability, providing a feasible pharmacological target for neuronal hyperexcitability management in neuropathic pain.

physiology↗

bioRxiv2021

Stingless bee floral visitation in the global tropics and subtropics

Bees play a key role in maintaining healthy terrestrial ecosystems by pollinating plants. Stingless bees (Apidae: Meliponini) are a diverse clade of social bees (>500 species) with a pantropical distribution spanning South and Central America, Africa, India, Australia and Asia. They are garnering increasing attention as commercially-beneficial pollinators of some crops, yet their contribution to the pollination of native plants in the tropics and subtropics remains poorly understood. Here we conduct a global review of the plants visited by stingless bees. We compile a database of reported associations (flower visits) between stingless bees and plants, from studies that have made either direct observations of foraging bees or analysed the pollen stored in nests. Worldwide, we find stingless bees have been reported to visit the flowers of plants from at least 220 different families and 1465 genera, with frequently reported interactions for many of the tropics most species-diverse plant families including Fabaceae, Asteraceae, Rubiaceae, Malvaceae, Lamiaceae, Arecaceae, Euphorbiaceae, Poaceae, Apocinaceae, Bignoniaceae, Melastomataceae and Myrtaceae. The list of commonly-visited plant families was similar for the stingless bee fauna of each of three major biogeographic regions (Neotropical, Afrotropical and Indo-Malayan-Australasian), though we detected differences in the proportional use of plant families by the stingless bees of the Indo-Malayan-Australasian and Neotropical regions, likely reflecting differences in the available flora of those regions. Stingless bees in all regions visit a range of exotic species in their preferred plant families (crops, ornamental plants and weeds), in addition to native plants. Although most reports of floral visitation on wild plants do not confirm effective pollen transfer, it is likely that stingless bees make at least some contribution to pollination for the majority of plants they visit. In all, our database supports the view that stingless bees play an important role in the ecosystems of the global tropics and subtropics as pollinators of an exceptionally large and diverse number of plants. This database also highlights important gaps in our knowledge of stingless bee resource use that may help focus future research efforts.

ecology↗