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J Virol ; 97(10): e0124123, 2023 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-37772824

RESUMO

IMPORTANCE: CD34+ hematopoietic progenitor cells (HPCs) are an important cellular reservoir for latent human cytomegalovirus (HCMV). Several HCMV genes are expressed during latency that are involved with the maintenance of the viral genome in CD34+ HPC. However, little is known about the process of viral reactivation in these cells. Here, we describe a viral protein, pUL8, and its interaction and stabilization with members of the Wnt/ß-catenin pathway as an important component of viral reactivation. We further define that pUL8 and ß-catenin interact with DVL2 via a PDZ-binding domain, and loss of UL8 interaction with ß-catenin-DVL2 restricts viral reactivation. Our findings will be instrumental in understanding the molecular processes involved in HCMV reactivation in order to design new antiviral therapeutics.


Assuntos
Antígenos CD34 , Citomegalovirus , Proteínas Desgrenhadas , Células-Tronco Hematopoéticas , Proteínas Virais , Ativação Viral , beta Catenina , Humanos , Antígenos CD34/metabolismo , beta Catenina/química , beta Catenina/metabolismo , Citomegalovirus/genética , Citomegalovirus/fisiologia , Proteínas Desgrenhadas/química , Proteínas Desgrenhadas/metabolismo , Células-Tronco Hematopoéticas/metabolismo , Células-Tronco Hematopoéticas/virologia , Domínios PDZ , Proteínas Virais/química , Proteínas Virais/metabolismo , Latência Viral/genética
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