The avian retroviral receptor Tva mediates the uptake of transcobalamin bound vitamin B12 (cobalamin)
| Autor: | Sergey N. Fedosov, Josef Geryk, Dana Kučerová, Markéta Reinišová, Cyril Bařinka, Jiří Hejnar, Jana Mikešová, Jan Kosla, Veronika Krchlíková, Daniel Elleder, Ebba Nexo |
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| Rok vydání: | 2021 |
| Předmět: |
receptor
Immunology Cell Chicken Cells Biology Microbiology Virus 03 medical and health sciences 0302 clinical medicine Transcobalamin Virology hemic and lymphatic diseases medicine cobalamin Receptor 030304 developmental biology 0303 health sciences Wild type Transmembrane protein Cell biology Virus-Cell Interactions retrovirus medicine.anatomical_structure Cell culture 030220 oncology & carcinogenesis Insect Science avian leukosis virus |
| Zdroj: | J Virol Krchlíková, V, Mikešová, J, Geryk, J, Bařinka, C, Nexo, E, Fedosov, S N, Kosla, J, Kučerová, D, Reinišová, M, Hejnar, J & Elleder, D 2021, ' The avian retroviral receptor tva mediates the uptake of transcobalamin bound vitamin B 12 (Cobalamin) ', Journal of Virology, vol. 95, no. 8, e02136-20 . https://doi.org/10.1128/JVI.02136-20 |
| ISSN: | 1098-5514 |
| DOI: | 10.1128/JVI.02136-20 |
| Popis: | The avian sarcoma and leukosis viruses (ASLVs) are important chicken pathogens. Some of the virus subgroups, including ASLV-A and K, utilize the Tva receptor for cell entrance. Though Tva was identified 3 decades ago, its physiological function remains unknown. Previously, we have noted an intriguing resemblance and orthology between the chicken gene coding for Tva and the human gene coding for CD320, a receptor involved in cellular uptake of transcobalamin (TC) in complex with vitamin B12/cobalamin (Cbl). Here, we show that both the transmembrane and the glycosylphosphatidylinositol (GPI)-anchored form of Tva in the chicken cell line DF-1 promotes the uptake of Cbl with the help of expressed and purified chicken TC. The uptake of TC-Cbl complex was monitored using an isotope-or fluorophore-labeled Cbl. We show that (i) TC-Cbl is internalized in chicken cells, and (ii) the uptake is lower in the Tva-knockout cells and higher in Tva-overexpressing cells when compared with that of wild-type chicken cells. The relation between physiological function of Tva and its role in infection was elaborated by showing that infection with ASLV subgroups (targeting Tva) impairs the uptake of TC-Cbl, while this is not the case for cells infected with ASLV-B (not recognized by Tva). In addition, exposure of the cells to a high concentration of TC-Cbl alleviates the infection with Tva-dependent ASLV.IMPORTANCE We demonstrate that the ASLV receptor Tva participates in the physiological uptake of TC-Cbl because the viral infection suppresses the uptake of Cbl and vice versa. Our results pave the road for future studies addressing the following issues: (i) whether a virus infection can be inhibited by TC-Cbl complexes in vivo, and (ii) whether any human virus employs the human TC-Cbl receptor CD320. In broader terms, our study sheds light on the intricate interplay between physiological roles of cellular receptors and their involvement in virus infection. |
| Databáze: | OpenAIRE |
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