Signatures of host–pathogen evolutionary conflict reveal MISTR—A conserved MItochondrial STress Response network

Host–pathogen conflicts leave genetic signatures in genes that are critical for host defense functions. Using these “molecular scars” as a guide to discover gene functions, we discovered a vertebrate-specific MItochondrial STress Response (MISTR) circuit. MISTR proteins are associated with electron transport chain (ETC) factors and activated by stress signals such as interferon gamma (IFNγ) and hypoxia. Upon stress, ultraconserved microRNAs (miRNAs) down-regulate MISTR1(NDUFA4) followed by replacement with paralogs MItochondrial STress Response AntiViral (MISTRAV) and/or MItochondrial STress Response Hypoxia (MISTRH). While cells lacking MISTR1(NDUFA4) are more sensitive to chemical and viral apoptotic triggers, cells lacking MISTRAV or expressing the squirrelpox virus-encoded vMISTRAV exhibit resistance to the same insults. Rapid evolution signatures across primate genomes for MISTR1(NDUFA4) and MISTRAV indicate recent and ongoing conflicts with pathogens. MISTR homologs are also found in plants, yeasts, a fish virus, and an algal virus indicating ancient origins and suggesting diverse means of altering mitochondrial function under stress. The discovery of MISTR circuitry highlights the use of evolution-guided studies to reveal fundamental biological processes.

First report of dermatophilosis in wild European red squirrels (Sciurus vulgaris)

The carcases of two wild red squirrels (Sciurus vulgaris) from Anglesey, North Wales, which had severe skin lesions, were presented to the Animal and Plant Health Agency. One was found dead in December 2017 and the second was found moribund in January 2018 but died 2 hours later. Both were examined at postmortem. The affected skin consisted of raised, firm, crusty lesions with pale subcutaneous necrotic tissue over the head particularly the face, eyelids and forehead. In addition, one had similar lesions on the scrotal and perineal area and along one hind leg extending to the foot. Postmortem examination, bacteriology and histopathology confirmed the presence of disease due to Dermatophilus congolensis with typical gross and pathological lesions. Squirrelpox virus was not detected. Here, we report the first description of dermatophilosis in European red squirrels, another important differential diagnosis of skin disease in a nationally declining population.