Research focus: from immune responses in fruit flies to chickens resistant to avian influenza

A collection of publication highlights from the Edinburgh Infectious Diseases network over the past month.

Viruses in Laboratory Drosophila and Their Impact on Host Gene Expression

Summary: Researchers from the Institute of Ecology and Evolution have been studying Drosophila melanogaster otherwise known as the fruit fly or lesser fruit fly, as they have one of the best characterized antiviral immune responses among invertebrates.

Researchers have found ten known viruses—including five that have not been experimentally isolated—but no previously unknown viruses. Their analysis of host gene expression revealed that numerous genes were differentially expressed in flies that were naturally infected with a virus.

Kuyateh, O and Obbard, DJ Viruses. 2023 Aug 31;15(9):1849. doi: 10.3390/v15091849.

Scottish Index of Multiple Deprivation (SIMD) indicators as predictors of mortality among patients hospitalised with COVID-19 disease in the Lothian Region, Scotland during the first wave: a cohort study

Summary: Researchers from the University of Edinburgh recently conducted a study of Sars-CoV-2, the causative agent of COVID-19 which has led to more than 226,000 deaths in the UK and multiple risk factors for mortality including age, sex and deprivation have been identified. This study aimed to identify which individual indicators of the Scottish Index of Multiple Deprivation (SIMD), an area-based deprivation index, were predictive of mortality.

The research found that SIMD, as an aggregate measure of deprivation, was not predictive of mortality in their cohort when other exposure measures were accounted for. However, they identified a two-fold increased risk of mortality in patients residing in areas with greater income-deprivation and/or number of hospitalisations due to alcohol.

Scopazzini, M.S., Cave, R.N.R., Mutch, C.P. et al Int J Equity Health. 205 (2023). https://doi.org/10.1186/s12939-023-02017-y

Cellular heterogeneity of the developing worker honey bee (Apis mellifera) pupa: a single cell transcriptomics analysis

Summary: Researchers for the Roslin Institute, the Centre for Inflammation Research and the Institute of Immunology and Infection have been looking at the developmental stages of the worker honey bee and have sought to determine their gene expression signatures.

Researchers examined the cell-to-cell network based on the similarity of the single-cells transcriptomic profiles. This is the first whole single-cell atlas of honey bees at any stage of development and demonstrates the potential for further work.

Patir A, Raper A, Fleming R, Henderson BEP, Murphy L, Henderson NC, Clark EL, Freeman TC, Barnett MW. G3 (Bethesda). 2023 Sep 30;13(10):jkad178. doi: 10.1093/g3journal/jkad178

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Natural immunity to malaria preferentially targets the endothelial protein C receptor-binding regions of PfEMP1s

Summary: Researchers from the Centre for Immunity, Infection and Evolution and the Institute for Immunology and Infection have been looking at antibody responses to variant surface antigens (VSA) produced by the malaria parasite determining that these may contribute to age-related natural immunity to severe malaria. Researchers looked at one VSA family that includes a subset of proteins that binds endothelial protein C receptor (EPCR) in human hosts.

They found that natural immunity to malaria targets specific regions within the EPCR-binding domain, particularly peptides containing EPCR-binding residues.

Tewey MA, Coulibaly D, Lawton JG, Stucke EM, Zhou AE, Berry AA, Bailey JA, Pike A, Dara A, Ouattara A, Lyke KE, Ifeonu O, Laurens MB, Adams M, Takala-Harrison S, Niangaly A, Kouriba B, Koné AK, Rowe JA, Doumbo OK, Patel JJ, Tan JC, Felgner PL, Plowe CV, Thera MA, Travassos MA. mSphere. 2023 Oct 24;8(5):e0045123. doi: 10.1128/msphere.00451-23.

The developmental hierarchy and scarcity of replicative slender trypanosomes in blood challenges their role in infection maintenance

Summary: Researchers from the School of Biological Sciences found that the development of trypanosomes to the stumpy forms entails terminal developmental arrest in the mammalian host. 

Suprisingly, and contrary to expection, their findings also suggest that that regardless of parasite morphology – slender or stumpy – the bloodstream parasite population has an insignificant role in the maintenance of the infection, and instead is devoted to transmission. 

Larcombe SD, Briggs EM, Savill N, Szoor B, Matthews KR. Proc Natl Acad Sci U S A. 2023 Oct 17;120(42):e2306848120. doi: 10.1073/pnas.2306848120.

Burden of respiratory syncytial virus-associated acute respiratory infections during pregnancy

Summary: Researchers from the Centre for Global Health at the Usher Institute have been looking into RSV associated acute respiratory infections during pregnancy.

They investigated 11 studies with pregnant individuals and found that among the 8126 individuals, the proportion with respiratory infections that tested positive for RSV ranged from 0.9% to 10.7%.  Amongst other findings, in three studies comparing RSV-positive and RSV-negative pregnant individuals found no difference in the odds of miscarriage, stillbirth, low birth weight, and small for gestational age. However RSV-positive pregnant people had higher odds of preterm delivery.

Kenmoe S, Chu HY, Dawood FS, Milucky J, Kittikraisak W, Matthewson H, Kulkarni D, Suntarattiwong P, Frivold C, Mohanty S, Havers F, Li Y, Nair H; for PROMISE investigators. J Infect Dis. 2023 Oct 12:jiad449. doi: 10.1093/infdis/jiad449.

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Creating resistance to avian influenza infection through genome editing of the ANP32 gene family

Summary: Researchers from the Roslin Institute and the Royal (Dick) School of Veterinary Studies have been investigating chickens who are genetically resistant to avian influenza, adn exploring how these chickens could prevent future outbreaks.

Their findings show that generating influenza A virus (IAV) resistant chickens with multiple genetic modifications will be required to curtail viral escape.

Idoko-Akoh A, Goldhill DH, Sheppard CM, Bialy D, Quantrill JL, Sukhova K, Brown JC, Richardson S, Campbell C, Taylor L, Sherman A, Nazki S, Long JS, Skinner MA, Shelton H, Sang HM, Barclay WS, McGrew MJ. Nat Commun. 2023 Oct 10;14(1):6136. doi: 10.1038/s41467-023-41476-3. 

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A systematic analysis of the human immune response to Plasmodium vivax

Summary: Researchers from the Institute of Immunology and Infection Research have been looking into the human immune response to Plasmodium vivax a parasite and human pathogen which is the most frequent cause of recurring malaria.

How Plasmodium vivax shapes the immune response to infection remains unclear and thus researchers inoculated human volunteers with the Plasmodium vivax and tracked their response through infection and convalescence.

Bach FA, Muñoz Sandoval D, Mazurczyk M, Themistocleous Y, Rawlinson TA, Harding AC, Kemp A, Silk SE, Barrett JR, Edwards NJ, Ivens A, Rayner JC, Minassian AM, Napolitani G, Draper SJ, Spence PJ. J Clin Invest. 2023 Oct 16;133(20):e152463. doi: 10.1172/JCI152463. 

Read the paper via PubMed