RAPID ADAPTIVE EVOLUTION OF AVIAN LEUKOSIS VIRUS TO BIOTECHNOLOGICALLY INDUCED HOST RESISTANCE

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F23%3A00580716" target="_blank" >RIV/68378050:_____/23:00580716 - isvavai.cz</a>

Výsledek na webu

<a href="http://ccsss.cz/index.php/ccsss/issue/view/41" target="_blank" >http://ccsss.cz/index.php/ccsss/issue/view/41</a>

DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

RAPID ADAPTIVE EVOLUTION OF AVIAN LEUKOSIS VIRUS TO BIOTECHNOLOGICALLY INDUCED HOST RESISTANCE

Popis výsledku v původním jazyce

Recently, chickens resistant to avian leucosis virus subgroup J (ALV-J) were developed by deleting a single amino acid, W38, in the ALV-J receptor NHE1 using the CRISPR/Cas9 technique1. This resistance was confirmed both in vitroand in vivo, and W38-/-chicken embryonic fibroblasts (CEF) displayed resistance to all tested virus strains in vitro. However, viruses evolve very rapidly, and the capacity of ALV-J adaptation to the resistant receptor warrants further investigation.We established reporter virus-based assay to select for adapted ALV-J variants. We assumed that escape mutations within the envelope protein could overcome cellular resistance in vitro. In accordance with this assumption, we isolated numerous escape virus variants and sequencing of their envgenes revealed eight single nucleotide substitution mutations. To confirm the adaptive capacity of these substitutions, we introduced these mutations into a retroviral vector RCASBP(J)GFP and tested the virus entry into cells with modified receptor. All eight variants replicated effectively in vitro in W38-/-CEFs. Notably, two of these variants successfully induced tumors in W38-/-chickens.Our results illustrate that cellular resistance, ensured by minor receptor modifications, can be overcome by a single nucleotide mutation that evolves rapidly in ALV-J

Název v anglickém jazyce

RAPID ADAPTIVE EVOLUTION OF AVIAN LEUKOSIS VIRUS TO BIOTECHNOLOGICALLY INDUCED HOST RESISTANCE

Popis výsledku anglicky

Recently, chickens resistant to avian leucosis virus subgroup J (ALV-J) were developed by deleting a single amino acid, W38, in the ALV-J receptor NHE1 using the CRISPR/Cas9 technique1. This resistance was confirmed both in vitroand in vivo, and W38-/-chicken embryonic fibroblasts (CEF) displayed resistance to all tested virus strains in vitro. However, viruses evolve very rapidly, and the capacity of ALV-J adaptation to the resistant receptor warrants further investigation.We established reporter virus-based assay to select for adapted ALV-J variants. We assumed that escape mutations within the envelope protein could overcome cellular resistance in vitro. In accordance with this assumption, we isolated numerous escape virus variants and sequencing of their envgenes revealed eight single nucleotide substitution mutations. To confirm the adaptive capacity of these substitutions, we introduced these mutations into a retroviral vector RCASBP(J)GFP and tested the virus entry into cells with modified receptor. All eight variants replicated effectively in vitro in W38-/-CEFs. Notably, two of these variants successfully induced tumors in W38-/-chickens.Our results illustrate that cellular resistance, ensured by minor receptor modifications, can be overcome by a single nucleotide mutation that evolves rapidly in ALV-J

Druh

O - Ostatní výsledky

CEP obor

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OECD FORD obor

10607 - Virology

Projekt

<a href="/cs/project/LX22NPO5103" target="_blank" >LX22NPO5103: Národní institut virologie a bakteriologie</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2023

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů