Disrupting the Amblyomma americanum (L.) CD147 receptor homolog prevents ticks from feeding to repletion and blocks spontaneous detachment of ticks from their host |
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| Authors: | Albert Mulenga Rabuesak Khumthong |
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| Institution: | 1. Center for Experimental and Molecular Medicine, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands;2. Experimental Virology, Academic Medical Center, University of Amsterdam, Amsterdam, 1105 AZ, The Netherlands;3. Department of Medical Microbiology, Onze Lieve Vrouwe Gasthuis, Amsterdam, 1091 AC, The Netherlands;4. Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06420, USA;1. National Institute of Health Dr. Ricardo Jorge, Águas de Moura, Portugal;2. Department of Pathology and Center for Biodefense and Emerging Infectious Diseases, The University of Texas Medical Branch, Galveston, TX, USA;3. Department of Veterinary Medicine, Universidade de Évora, Évora, Portugal;1. Infectious Diseases Department, Hospital San Pedro-CIBIR, Logroño, Spain;2. The Pirbright Institute, Pirbright, Surrey, UK;1. Department of Animal Pathology, Faculty of Veterinary Medicine, University of Zaragoza, Spain;2. Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK 74078, USA;3. SaBio, Instituto de Investigación en Recursos Cinegéticos (IREC)–Consejo Superior de Investigaciones Científicas (CSIC)–Universidad de Castilla–La Mancha (UCLM)-Junta de Comunidades de Castilla–La Mancha (JCCM), Ronda de Toledo s/n, 13005 Ciudad Real, Spain;4. Center for Infection and Immunity of Lille (CIIL), INSERM U1019–CNRS UMR 8204, Université Lille Nord de France, Institut Pasteur de Lille, Lille, France;1. Centre for Comparative Genomics, Murdoch University, WA 6151, Australia;2. USDA-ARS Knipling-Bushland US Livestock Insects Research Laboratory and Veterinary Pest Genomics Center, 2700 Fredericksburg Rd., Kerrville, TX 78028, USA;3. National Center for Genome Resources, Santa Fe, NM, USA;4. USDA-ARS Cattle Fever Tick Research Laboratory, 22675 North Moorefield Rd., Edinburg, TX 78541, USA;5. Amplicon Express, Pullman, WA, USA;6. Centre for Crop Disease and Management, Curtin University, Bentley, WA 6102, Australia |
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| Abstract: | The CD147 receptor is a cell-surface glycoprotein in the IgG family that plays pivotal roles in intercellular interactions involved with numerous physiological and pathological processes such as extracellular matrix remodeling. We previously found an Amblyomma americanum (Aam) tick CD147 receptor homolog among genes that were up regulated in response to tick feeding stimuli. This study characterizes an AamCD147 receptor protein that is 72–83% conserved in other tick species and possess characteristic CD147 receptor sequence features: an extracellular (EC) region containing two IgG domains, a transmembrane and the cytoplasmic domains. Likewise, the AamCD147 EC domain folds into secondary structures that are consistent to the human homolog: an amino-terminus β-barrel that is linked to 2-carboxy-terminus β-sheets with consensus disulfide bonds conserved in each of the 2 domains. CD147 receptor signaling and regulatory mechanisms are putatively conserved in ticks as revealed by in silico analysis that show presence in the tick genome of CD147 receptor signaling protein homologs, cyclophilin (CyP) A and B, and chaperones that transport it to the plasma membrane, caveolin-1 and CyP60. The AamCD147 receptor has a dichotomous expression pattern of where it is up regulated in response to feeding in the salivary gland but remains constant at the midgut and ovary levels suggesting that it may regulate different functions in different tick organs. We speculate that biological functions of the AamCD147 receptor are essential to tick feeding success as revealed by RNAi-mediated silencing that caused ticks to obtain smaller blood meals, of which ～69% were below threshold to trigger spontaneous detachment of ticks from the host. These ticks showed unusual cuticle tenderness and assumed a reddish coloration, a phenomenon that has been attributed to tick midgut damage allowing red blood cells to leak into tick hemolymph. On the basis of the CD147 receptor being linked to tissue growth regulation in mammals, we speculate that silencing of the AamCD147 receptor blocked progression of the tick intermolt growth, a process that precedes tick engorgement and their spontaneous detachment of from the host to end feeding. The results are discussed in context of advances in tick molecular physiology. |
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