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@article{1764656,
author = {Procházková, Michaela and Füzik, Tibor and Grybchuk, Danyil and Falginella, Francesco Luca and Podešvová, Lucie and Yurchenko, Vyacheslav and Vácha, Robert and Plevka, Pavel},
article_number = {3},
doi = {http://dx.doi.org/10.1128/JVI.01957-20},
keywords = {virus; Leishmania; Viannia; leishmaniasis; parasite; RNA; LRV1; Totiviridae; virion; structure; cryo-electron microscopy; capsid; genome; uncoating; mRNA; CAP-4; decapping},
language = {eng},
issn = {0022-538X},
journal = {Journal of Virology},
title = {Capsid Structure of Leishmania RNA Virus 1},
url = {https://jvi.asm.org/content/95/3/e01957-20},
volume = {95},
year = {2021}
}
TY - JOUR
ID - 1764656
AU - Procházková, Michaela - Füzik, Tibor - Grybchuk, Danyil - Falginella, Francesco Luca - Podešvová, Lucie - Yurchenko, Vyacheslav - Vácha, Robert - Plevka, Pavel
PY - 2021
TI - Capsid Structure of Leishmania RNA Virus 1
JF - Journal of Virology
VL - 95
IS - 3
SP - "e01957"
EP - "e01957"
PB - American Society for Microbiology
SN - 0022538X
KW - virus
KW - Leishmania
KW - Viannia
KW - leishmaniasis
KW - parasite
KW - RNA
KW - LRV1
KW - Totiviridae
KW - virion
KW - structure
KW - cryo-electron microscopy
KW - capsid
KW - genome
KW - uncoating
KW - mRNA
KW - CAP-4
KW - decapping
UR - https://jvi.asm.org/content/95/3/e01957-20
N2 - Leishmania parasites cause a variety of symptoms, including mucocutaneous leishmaniasis, which results in the destruction of the mucous membranes of the nose, mouth, and throat. The species of Leishmania carrying Leishmania RNA virus 1 (LRV1), from the family Totiviridae, are more likely to cause severe disease and are less sensitive to treatment than those that do not contain the virus. Although the importance of LRV1 for the severity of leishmaniasis was discovered a long time ago, the structure of the virus remained unknown. Here, we present a cryo-electron microscopy reconstruction of the virus-like particle of LRV1 determined to a resolution of 3.65 angstrom. The capsid has icosahedral symmetry and is formed by 120 copies of a capsid protein assembled in asymmetric dimers. RNA genomes of viruses from the family Totiviridae are synthetized, but not capped at the 5' end, by virus RNA polymerases. To protect viral RNAs from degradation, capsid proteins of the L-A totivirus cleave the 5' caps of host mRNAs, creating decoys to overload the cellular RNA quality control system. Capsid proteins of LRV1 form positively charged clefts, which may be the cleavage sites for the 5' cap of Leishmania mRNAs. The putative RNA binding site of LRV1 is distinct from that of the related L-A virus. The structure of the LRV1 capsid enables the rational design of compounds targeting the putative decapping site. Such inhibitors may be developed into a treatment for mucocutaneous leishmaniasis caused by LRV1-positive species of Leishmania. IMPORTANCE Twelve million people worldwide suffer from leishmaniasis, resulting in more than 30 thousand deaths annually. The disease has several variants that differ in their symptoms. The mucocutaneous form, which leads to disintegration of the nasal septum, lips, and palate, is caused predominantly by Leishmania parasites carrying Leishmania RNA virus 1 (LRV1). Here, we present the structure of the LRV1 capsid determined using cryo-electron microscopy. Capsid proteins of a related totivirus, L-A virus, protect viral RNAs from degradation by cleaving the 5' caps of host mRNAs. Capsid proteins of LRV1 may have the same function. We show that the LRV1 capsid contains positively charged clefts that may be sites for the cleavage of mRNAs of Leishmania cells. The structure of the LRV1 capsid enables the rational design of compounds targeting the putative mRNA cleavage site. Such inhibitors may be used as treatments for mucocutaneous leishmaniasis.
ER -
PROCHÁZKOVÁ, Michaela, Tibor FÜZIK, Danyil GRYBCHUK, Francesco Luca FALGINELLA, Lucie PODEŠVOVÁ, Vyacheslav YURCHENKO, Robert VÁCHA and Pavel PLEVKA. Capsid Structure of Leishmania RNA Virus 1. \textit{Journal of Virology}. American Society for Microbiology, 2021, vol.~95, No~3, p.~''e01957'', 12 pp. ISSN~0022-538X. Available from: https://dx.doi.org/10.1128/JVI.01957-20.
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