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.

Basic information

Original name

Capsid Structure of Leishmania RNA Virus 1

Authors

PROCHÁZKOVÁ, Michaela (203 Czech Republic, belonging to the institution), Tibor FÜZIK (703 Slovakia, belonging to the institution), Danyil GRYBCHUK (804 Ukraine, belonging to the institution), Francesco Luca FALGINELLA (380 Italy, belonging to the institution), Lucie PODEŠVOVÁ, Vyacheslav YURCHENKO, Robert VÁCHA (203 Czech Republic, belonging to the institution) and Pavel PLEVKA (203 Czech Republic, guarantor, belonging to the institution)

Edition

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

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10607 Virology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 6.549

RIV identification code

RIV/00216224:14740/21:00121505

Organization unit

Central European Institute of Technology

DOI

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

UT WoS

000609185100014

Keywords in English

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

Abstract

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.

Links

LM2015085, research and development project

Name: CERIT Scientific Cloud (Acronym: CERIT-SC)

Investor: Ministry of Education, Youth and Sports of the CR, CERIT Scientific Cloud

LM2018140, research and development project

Name: e-Infrastruktura CZ (Acronym: e-INFRA CZ)

Investor: Ministry of Education, Youth and Sports of the CR

LQ1601, research and development project

Name: CEITEC 2020 (Acronym: CEITEC2020)

Investor: Ministry of Education, Youth and Sports of the CR

3041, interní kód MU

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

Investor: EMBO (European Molecular Biology Organization)

90042, large research infrastructures

Name: CESNET II

90127, large research infrastructures

Name: CIISB II

Citovat

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. 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.

@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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