• Broad host range of SARS-CoV-2 predicted by comparative and structural analysis of ACE2 in vertebrates

      Damas, Joana; Hughes, Graham M.; Keough, Kathleen C.; Painter, Corrie A.; Persky, Nicole S.; Corbo, Marco; Hiller, Michael; Koepfli, Klaus-Peter; Pfenning, Andreas R.; Zhao, Huabin; et al. (2020)
      The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of COVID-19. The main receptor of SARS-CoV-2, angiotensin I converting enzyme 2 (ACE2), is now undergoing extensive scrutiny to understand the routes of transmission and sensitivity in different species. Here, we utilized a unique dataset of ACE2 sequences from 410 vertebrate species, including 252 mammals, to study the conservation of ACE2 and its potential to be used as a receptor by SARS-CoV-2. We designed a five-category binding score based on the conservation properties of 25 amino acids important for the binding between ACE2 and the SARS-CoV-2 spike protein. Only mammals fell into the medium to very high categories and only catarrhine primates into the very high category, suggesting that they are at high risk for SARS-CoV-2 infection. We employed a protein structural analysis to qualitatively assess whether amino acid changes at variable residues would be likely to disrupt ACE2/SARS-CoV-2 spike protein binding and found the number of predicted unfavorable changes significantly correlated with the binding score. Extending this analysis to human population data, we found only rare (frequency <0.001) variants in 10/25 binding sites. In addition, we found significant signals of selection and accelerated evolution in the ACE2 coding sequence across all mammals, and specific to the bat lineage. Our results, if confirmed by additional experimental data, may lead to the identification of intermediate host species for SARS-CoV-2, guide the selection of animal models of COVID-19, and assist the conservation of animals both in native habitats and in human care.
    • Human and great ape red blood cells differ in plasmalogen levels and composition

      Moser, A.B.; Steinberg, S.J.; Watkins, P.A.; Moser, H.W.; Ramaswamy, K.; Siegmund, K.D.; Lee, D.R.; Ely, J.J.; Ryder, Oliver A.; Hacia, J.G. (2011)
      Plasmalogens are ether phospholipids required for normal mammalian developmental, physiological, and cognitive functions. They have been proposed to act as membrane antioxidants and reservoirs of polyunsaturated fatty acids as well as influence intracellular signaling and membrane dynamics. Plasmalogens are particularly enriched in cells and tissues of the human nervous, immune, and cardiovascular systems. Humans with severely reduced plasmalogen levels have reduced life spans, abnormal neurological development, skeletal dysplasia, impaired respiration, and cataracts. Plasmalogen deficiency is also found in the brain tissue of individuals with Alzheimer disease.
    • Immunomics of the koala (Phascolarctos cinereus)

      Abts, Kendra C.; Ivy, Jamie A.; DeWoody, J. Andrew (2015)
      The study of the koala transcriptome has the potential to advance our understanding of its immunome—immunological reaction of a given host to foreign antigens—and to help combat infectious diseases (e.g., chlamydiosis) that impede ongoing conservation efforts….. Our efforts have produced full-length sequences for potentially important immune genes in koala, which should serve as targets for future investigations that aim to conserve koala populations.
    • Intergenerational effects of nutrition on immunity: a systematic review and meta-analysis

      Grueber, Catherine E.; Gray Lindsey J.; Morris Katrina M.; Simpson Stephen J.; Senior Alistair M. (2017)
      ...Using the geometric framework for nutrition (a method for analysing diet compositions wherein food nutrient components are expressed as axes in a Cartesian coordinate space) to define dietary manipulations in terms of their energy and macronutrient compositions, we compiled the results of 226 experiments from 38 published papers on the intergenerational effects of diet on immunity, across a range of study species and immunological responses. We observed intergenerational impacts of parental nutrition on a number of offspring immunological processes, including expression of pro‐inflammatory biomarkers as well as decreases in anti‐inflammatory markers in response to certain parental diets....
    • Lack of genetic diversity across diverse immune genes in an endangered mammal, the Tasmanian devil (Sarcophilus harrisii)

      Morris, K.M.; Wright, B.; Grueber, Catherine E.; Hogg, Carolyn J.; Belov, Katherine (2015)
      The Tasmanian devil (S arcophilus harrisii ) is threatened with extinction due to the spread of devil facial tumour disease. Polymorphisms in immune genes can provide adaptive potential to resist diseases. Previous studies in diversity at immune loci in wild species have almost exclusively focused on genes of the major histocompatibility complex (MHC ); however, these genes only account for a fraction of immune gene diversity. Devils lack diversity at functionally important immunity loci, including MHC and Toll‐like receptor genes. Whether there are polymorphisms at devil immune genes outside these two families is unknown. Here, we identify polymorphisms in a wide range of key immune genes, and develop assays to type single nucleotide polymorphisms (SNP s) within a subset of these genes. A total of 167 immune genes were examined, including cytokines, chemokines and natural killer cell receptors. Using genome‐level data from ten devils, SNP s within coding regions, introns and 10 kb flanking genes of interest were identified. We found low polymorphism across 167 immune genes examined bioinformatically using whole‐genome data. From this data, we developed long amplicon assays to target nine genes. These amplicons were sequenced in 29–220 devils and found to contain 78 SNP s, including eight SNPS within exons. Despite the extreme paucity of genetic diversity within these genes, signatures of balancing selection were exhibited by one chemokine gene, suggesting that remaining diversity may hold adaptive potential. The low functional diversity may leave devils highly vulnerable to infectious disease, and therefore, monitoring and preserving remaining diversity will be critical for the long‐term management of this species. Examining genetic variation in diverse immune genes should be a priority for threatened wildlife species. This study can act as a model for broad‐scale immunogenetic diversity analysis in threatened species.
    • Pandemic (H1N1) 2009 virus in 3 wildlife species, San Diego, California, USA

      Schrenzel, Mark D.; Tucker, Tammy A.; Stalis, Ilse H.; Kagan, Rebecca A.; Burns, Russell P.; Denison, Amy M.; Drew, Clifton P.; Paddock, Christopher D.; Rideout, Bruce (2011)
      The influenza A pandemic (H1N1) 2009 virus rapidly created a global pandemic among humans and also appears to have strong infectivity for a broad range of animal species (1–3). The virus has been found repeatedly in swine and has been detected in a dog, cats, turkeys, and domestic ferrets and in nondomestic animals, including skunks, cheetahs, and giant anteaters (2–4). In some cases, animal-to-animal transmission may have occurred, raising concern about the development of new wildlife reservoirs. In 2009, the first recognized occurrence of pandemic (H1N1) 2009 in southern California in April was followed by a surge of cases during October through November (4). During this time, respiratory illness developed in a 12-year-old male American badger (Taxidea taxus taxus), a 19-year-old female Bornean binturong (Arctictis binturong penicillatus), and a 7-year-old black-footed ferret (Mustela nigripes) housed in a San Diego zoological garden....
    • Quantitative indirect ELISA-based method for the measurement of serum IgG in springbok calves

      Coons, David M.; Thompson, Kimberly A.; Lamberski, Nadine; Chigerwe, Munashe (2012)
      ...In this study we describe a method for measuring sera immunoglobulin levels using an indirect enzyme-linked immunosorbent assay (ELISA) that can be completed within one working day. The described method is relatively more accurate, precise, and expeditious and less labor intensive than an RID assay. While this protocol was developed for use with springbok sera, it should be easily adaptable for other non-domestic ruminants species for which commercial antibodies are not readily available....
    • Wildlife-microbiome interactions and disease: Exploring opportunities for disease mitigation across ecological scales

      Williams, Candace L.; Caraballo-Rodríguez, Andrés Mauricio; Allaband, Celeste; Zarrinpar, Amir; Knight, Rob; Gauglitz, Julia M. (2018)
      … we will examine how the microbiome influences gastrointestinal disorders, metabolic dysregulation, reproduction, and disease susceptibility in captive wildlife. Investigation of wildlife, and specifically captive wildlife, affords a unique opportunity to gain understanding of the broad diversity of the associated microbiota and learn from nature’s molecular and microbial responses to disease. Studies like these could lead to the discovery of new interventions, ranging from dietary changes to the use of microbes or their natural products as treatment…