Research focus: From Influenza to plant pathogens and global health

Summary:  Macrophages in various tissues have important roles in tissue homeostasis and defence against pathogens, particularly at mucosal barrier sites like the lung and gut. However, the fate and function of monocyte-derived macrophages during infection, injury, and inflammation are still debated.

This review by Calum Bain in the Centre for Inflammation Research explores the diverse functions of monocytes and their derivatives in the lung, ranging from combating infection to promoting tissue repair and potentially contributing to pathology.

T'Jonck W, Bain CC, Int J Biochem Cell Biol. 2023 Jun;159:106421. doi: 10.1016/j.biocel.2023.106421.

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Summary:  In a groundbreaking study, scientists from the Roslin Institute tested the effectiveness of CpG dinucleotide enrichment in the influenza A virus genome as a strategy for developing live attenuated vaccines. By engineering a vaccine strain with increased CpG content in a specific genome segment, they observed strong attenuation in mice, while still providing protection against a potentially lethal challenge dose of the wildtype virus. Furthermore, the CpG-enriched viruses demonstrated genetic stability during serial passage, indicating their potential as a realistic and economically viable platform to enhance existing live attenuated vaccines.

Sharp CS, Thompson BH, Nash TJ, Diebold O, Pinto RM, Thorley L, Lin Y, Sives S, Wise H, Clohisey Hendry SC, Grey F, Vervelde L, Simmonds P, Digard P, Gaunt ER, PLoS Pathog. 2023 May 5;19(5):e1011357. doi: 10.1371/journal.ppat.1011357.

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Summary: In a study involving the School of Biological Sciences, researchers explored the relationship between DNA methylation and sex-biased gene expression in the Asian citrus psyllid, the plant lice that is a significant carrier of Huanglongbing, or yellow dragon disease. They identified differences in gene expression and DNA methylation between male and female psyllids, shedding light on the development of pest control strategies using epigenetic approaches that could be beneficial for other agricultural insect pests.

Yu X , Marshall H, Liu Y, Xiong Y , Zeng X, Yu H, Chen W, Zhou G, Zhu B , Ross L, Lu Z, Evolution. 2023 Apr 27;77(5):1203-1215. doi: 10.1093/evolut/qpad036.

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Summary: Another study involving the School of Biological Sciences reveals a significant negative association between systemic inflammation, S. haematobium infections, and cognitive function in preschool-aged children (PSAC). Based on these findings, the researchers strongly recommend the incorporation of PSAC performance assessment into mass drug treatment programmes.

Kasambala M, Mukaratirwa S, Vengesai A, Mduluza-Jokonya T, Jokonya L, Midzi H, Makota RB, Mutemeri A, Maziti E, Dube-Marimbe B, Chibanda D, Mutapi F, Mduluza T, Front Immunol. 2023 Apr 18;14:1139912. doi: 10.3389/fimmu.2023.1139912.

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Summary: Quality assurance is essential in human papillomavirus (HPV) molecular testing-based cervical screening programs, especially in diverse settings such as low- and middle-income countries.

Kate Cuschieri's research from the Scottish Human Papillomavirus Reference Laboratory presents key recommendations for ensuring quality assurance in HPV screening, including the selection and implementation of an HPV screening test, establishing robust quality assurance systems, and ensuring staff competence, while acknowledging the challenges associated with implementing these recommendations in various settings.

Cuschieri K, Fellner MD, Arroyo Mühr LS, Padalko E, Correa RM, Dillner J, Gultekin M, Picconi MA, Int J Gynecol Cancer. 2023 May 1;33(5):802-811. doi: 10.1136/ijgc-2022-004197.

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Summary: HPV is important in cervical cancer. A study on Ghanaian women with cervical disease found various types of HPV, with HPV-16 being the most common. A specific variant called HPV-16C1 was prevalent. This emphasizes the need for vaccination to prevent cervical disease in Ghana.

The study from the Scottish HPV Reference Laboratory at the Royal Infirmary of Edinburgh is a starting point for understanding how vaccines can combat HPV infections and related illnesses.

Kaba G, Stevenson A, Sakyi SA, Konney TO, Bhatia R, Titiloye NA, Oppong SA, Agyemang-Yeboah F, Cuschieri K, Graham SV, Tumour Virus Res. 2023 May 11;15:200261. doi: 10.1016/j.tvr.2023.200261.

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Summary: Prof Sargison from The Royal (Dick) School of Veterinary Studies participated in a study on treating benzimidazole-resistant Haemonchus contortus in sheep. They explored combining Citrus aurantium var. Dulcis essential oil (CaEO) with albendazole (ABZ). In vitro tests determined effective concentrations, and sixteen sheep were involved in in vivo tests. The combination of CaEO and ABZ showed limited effectiveness, highlighting the impact of natural products on anthelmintic treatment.

Mesquita-Sousa D, Campos NRCL, Pereira JRF, Gomes MN, Silva CR, Cutrim-Júnior JAA , Brito DRB, Sampaio RM, Sargison ND, Lifschitz A, Costa-Junior LM, Vet Parasitol. 2023 Jun;318:109929. doi: 10.1016/j.vetpar.2023.109929.

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Summary: A research team from the Centre for Engineering Biology focuses on RNA-binding proteins (RBPs) and their role in governing transcript lifespan and adaptive responses in microbes. They propose using UV light to study protein-RNA interactions, providing comprehensive maps of RBPs and their interacting RNAs in living cells. This overview highlights prominent UV cross-linking techniques used to investigate RNA interactomes in microbes, guiding method selection and experimental design.

Esteban-Serna S, McCaughan H, Granneman S, Mol Microbiol. 2023 May 10. doi: 10.1111/mmi.15073.

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Summary: In November 2021, two new highly pathogenic avian influenza viruses (H5N1) were found in dead migratory birds in China. These viruses likely originated from wild birds traveling between Europe and Asia. Researchers from The Roslin Institute and China discovered that these viruses have a weak response to vaccine antiserum, posing serious risks to both poultry and public health.

Yang J, Zhang C, Yuan Y, Sun J, Lu L, Sun H, Sun H, Chu D, Qin S, Chen J, Zhang C, Hao X, Shi W, Liu W, Gao GF, Digard P, Lycett S, Bi Y, Emerg Infect Dis. 2023 Jun;29(6):1244-1249. doi: 10.3201/eid2906.221723.

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Summary: Researchers from the Centre for Inflammation Research were part of an international research team that conducted a phase 2 trial on COVID-19 patients. They tested the combination of spironolactone and dexamethasone.

The study involved 120 patients in Delhi, with 74 receiving the combination and 46 receiving dexamethasone alone. Although time to recovery did not significantly differ, the combination group showed improvements in D-dimer and aldosterone levels, more oxygen-free days, and better cough scores. Further phase 3 trials are needed to confirm these findings.

Wadhwa B, Malhotra V, Kerai S, Husain F, Pandey NB, Saxena KN, Singh V, Quinn TM, Li F, Gaughan E, Shankar-Hari M, Mills B, Antonelli J, Bruce A, Finlayson K, Moore A, Dhaliwal K, Edwards C, BMC Infect Dis. 2023 May 15;23(1):326. doi: 10.1186/s12879-023-08286-w.

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Summary: Prof Baillie, from the Centre for Inflammation Research and Roslin Institute, was involved in a study that investigated the hepatitis outbreak among Scottish children in 2022, which later spread to 35 countries. The study suggested a possible link between the outbreak and human adenovirus. Additionally, it revealed that adeno-associated virus 2 (AAV2) infection was associated with a genetic vulnerability to the disease. A significant number of hepatitis cases were found to have AAV2, along with a T cell immune response in liver samples. These findings provide insights into the outbreak of pediatric hepatitis related to AAV2 infection and highlight the role of host genetics in disease susceptibility.

Baillie JK at all, Nature. 2023 May;617(7961):555-563. doi: 10.1038/s41586-023-05948-2.

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