Host kinase regulation of Plasmodium vivax dormant and replicating liver stages.
| العنوان: | Host kinase regulation of Plasmodium vivax dormant and replicating liver stages. |
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| المؤلفون: | Glennon EK; Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA, USA., Wei L; Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA, USA., Roobsoong W; Mahidol Vivax Research Unit, Mahidol University, Bangkok, Thailand., Primavera VI; Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA, USA., Tongogara T; Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA, USA., Yee CB; Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA, USA., Sattabongkot J; Mahidol Vivax Research Unit, Mahidol University, Bangkok, Thailand., Kaushansky A; Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA, USA.; Department of Pediatrics, University of Washington, Seattle, WA, USA.; Department of Global Health, University of Washington, Seattle, WA, USA. |
| المصدر: | BioRxiv : the preprint server for biology [bioRxiv] 2023 Nov 13. Date of Electronic Publication: 2023 Nov 13. |
| نوع المنشور: | Preprint |
| اللغة: | English |
| بيانات الدورية: | Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE |
| مستخلص: | Upon transmission to the liver, Plasmodium vivax parasites form replicating schizonts, which continue to initiate blood-stage infection, or dormant hypnozoites that reactivate weeks to months after initial infection. P. vivax phenotypes in the field vary significantly, including the ratio of schizonts to hypnozoites formed and the frequency and timing of relapse. Evidence suggests that both parasite genetics and environmental factors underly this heterogeneity. We previously demonstrated that data on the effect of a panel of kinase inhibitors with overlapping targets on Plasmodium liver stage infection, in combination with a computational approach called kinase regression (KiR), can be used to uncover novel host regulators of infection. Here, we applied KiR to evaluate the extent to which P. vivax liver-stage parasites are susceptible to changes in host kinase activity. We identified a role for a subset of host kinases in regulating schizont and hypnozoite infection and schizont size and characterized overlap as well as variability in host phosphosignaling dependencies between parasite forms and across multiple patient isolates. Striking, our data point to variability in host dependencies across P. vivax isolates, suggesting one possible origin of the heterogeneity observed across P. vivax in the field. Competing Interests: Competing Interests The authors declare no competing interests. |
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| معلومات مُعتمدة: | R01 AI177257 United States AI NIAID NIH HHS; R21 AI151344 United States AI NIAID NIH HHS |
| تواريخ الأحداث: | Date Created: 20231128 Latest Revision: 20231212 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC10680662 |
| DOI: | 10.1101/2023.11.13.566868 |
| PMID: | 38014051 |
| قاعدة البيانات: | MEDLINE |
| DOI: | 10.1101/2023.11.13.566868 |
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