Capsid Structure of Leishmania RNA Virus 1

J 2021

Capsid Structure of Leishmania RNA Virus 1

PROCHÁZKOVÁ, Michaela, Tibor FÜZIK, Danyil GRYBCHUK, Francesco Luca FALGINELLA, Lucie PODEŠVOVÁ et. al.

Základní údaje

Originální název

Capsid Structure of Leishmania RNA Virus 1

Autoři

PROCHÁZKOVÁ, Michaela (203 Česká republika, domácí), Tibor FÜZIK (703 Slovensko, domácí), Danyil GRYBCHUK (804 Ukrajina, domácí), Francesco Luca FALGINELLA (380 Itálie, domácí), Lucie PODEŠVOVÁ, Vyacheslav YURCHENKO, Robert VÁCHA (203 Česká republika, domácí) a Pavel PLEVKA (203 Česká republika, garant, domácí)

Vydání

Journal of Virology, American Society for Microbiology, 2021, 0022-538X

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10607 Virology

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 6.549

Kód RIV

RIV/00216224:14740/21:00121505

Organizační jednotka

Středoevropský technologický institut

DOI

http://dx.doi.org/10.1128/JVI.01957-20

UT WoS

000609185100014

Klíčová slova anglicky

virus; Leishmania; Viannia; leishmaniasis; parasite; RNA; LRV1; Totiviridae; virion; structure; cryo-electron microscopy; capsid; genome; uncoating; mRNA; CAP-4; decapping

Štítky

CF BIC, CF CRYO, CF PROT, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 9. 10. 2024 12:59, Ing. Martina Blahová

Anotace

V originále

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.

Návaznosti

LM2015085, projekt VaV

Název: CERIT Scientific Cloud (Akronym: CERIT-SC)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, CERIT Scientific Cloud

LM2018140, projekt VaV

Název: e-Infrastruktura CZ (Akronym: e-INFRA CZ)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, e-Infrastruktura CZ

LQ1601, projekt VaV

Název: CEITEC 2020 (Akronym: CEITEC2020)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, CEITEC 2020

3041, interní kód MU

Název: Structural studies of human and animal pathogens from the order Picornavirales

Investor: EMBO (European Molecular Biology Organization), Structural studies of human and animal pathogens from the order Picornavirales

90042, velká výzkumná infrastruktura

Název: CESNET II

90127, velká výzkumná infrastruktura

Název: CIISB II

Citovat

PROCHÁZKOVÁ, Michaela, Tibor FÜZIK, Danyil GRYBCHUK, Francesco Luca FALGINELLA, Lucie PODEŠVOVÁ, Vyacheslav YURCHENKO, Robert VÁCHA a Pavel PLEVKA. Capsid Structure of Leishmania RNA Virus 1. Journal of Virology. American Society for Microbiology, 2021, roč. 95, č. 3, s. "e01957", 12 s. ISSN 0022-538X. Dostupné z: https://dx.doi.org/10.1128/JVI.01957-20.

@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 a Pavel PLEVKA. Capsid Structure of Leishmania RNA Virus 1. \textit{Journal of Virology}. American Society for Microbiology, 2021, roč.~95, č.~3, s.~''e01957'', 12 s. ISSN~0022-538X. Dostupné z: https://dx.doi.org/10.1128/JVI.01957-20.

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