Numb-associated kinases regulate sandfly-borne Toscana virus entry.

Autor:	Moalem Y; Department of Clinical Microbiology and Immunology, Faculty of Medical & Health Sciences, Tel Aviv University, Tel Aviv, Israel., Katz R; Department of Clinical Microbiology and Immunology, Faculty of Medical & Health Sciences, Tel Aviv University, Tel Aviv, Israel., Subramaniam AG; Department of Physiology and Pharmacology, Faculty of Medical & Health Sciences, Tel Aviv University, Tel Aviv, Israel., Malis Y; Department of Pathology, Faculty of Medical & Health Sciences, Tel Aviv University, Tel Aviv, Israel., Yaffe Y; The Drimmer-Fischler Family Stem Cell Core Laboratory for Regenerative Medicine, Tel Aviv University, Tel Aviv, Israel., Borenstein-Auerbach N; Department of Cell and Developmental Biology, Faculty of Medical & Health Sciences, Tel Aviv University, Tel Aviv, Israel., Tadmor K; Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel., Raved R; School of Neurobiology, Biochemistry and Biophysics, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel., Maoz BM; The Drimmer-Fischler Family Stem Cell Core Laboratory for Regenerative Medicine, Tel Aviv University, Tel Aviv, Israel.; Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.; Department of Biomedical Engineering, Tel Aviv University, Tel Aviv, Israel., Yoo JS; School of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University, Daegu, Republic of Korea., Lustig Y; Central Virology Laboratory, Ministry of Health, Chaim Sheba Medical Center, Tel Hashomer, Israel.; School of Public Health, School of Medicine, Tel Aviv University, Tel Aviv, Israel., Luxenburg C; Department of Cell and Developmental Biology, Faculty of Medical & Health Sciences, Tel Aviv University, Tel Aviv, Israel., Perlson E; Department of Physiology and Pharmacology, Faculty of Medical & Health Sciences, Tel Aviv University, Tel Aviv, Israel., Einav S; Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford University, Stanford, CA, USA.; Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA.; Chan Zuckerberg Biohub, San Francisco, CA, USA., Sklan EH; Department of Clinical Microbiology and Immunology, Faculty of Medical & Health Sciences, Tel Aviv University, Tel Aviv, Israel.
Jazyk:	angličtina
Zdroj:	Emerging microbes & infections [Emerg Microbes Infect] 2024 Dec; Vol. 13 (1), pp. 2382237. Date of Electronic Publication: 2024 Jul 26.
DOI:	10.1080/22221751.2024.2382237
Abstrakt:	Sandfly-borne Toscana virus (TOSV) is an enveloped tri-segmented negative single-strand RNA Phlebovirus . It is an emerging virus predominantly endemic in southwestern Europe and Northern Africa. Although TOSV infection is typically asymptomatic or results in mild febrile disease, it is neurovirulent and ranks among the three most common causes of summer meningitis in certain regions. Despite this clinical significance, our understanding of the molecular aspects and host factors regulating phlebovirus infection is limited. This study characterized the early steps of TOSV infection. Our findings reveal that two members of the Numb-associated kinases family of Ser/Thr kinases, namely adaptor-associated kinase 1 (AAK1) and cyclin G-associated kinase (GAK), play a role in regulating the early stages of TOSV entry. FDA-approved inhibitors targeting these kinases demonstrated significant inhibition of TOSV infection. This study suggests that AAK1 and GAK represent druggable targets for inhibiting TOSV infection and, potentially, related Phleboviruses .
Databáze:	MEDLINE
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