Downregulation of Cell Surface Major Histocompatibility Complex Class I Expression Is Mediated by the Left-End Transcription Unit of Fowl Adenovirus 9

Major histocompatibility complex class I (MHC-I) molecules play a critical role in the host’s antiviral response by presenting virus-derived antigenic peptides to cytotoxic T lymphocytes (CTLs), enabling the clearance of virus-infected cells. Human adenoviruses evade CTL-mediated cell lysis, in part...

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Autores principales:	Bryan D. Griffin, Juan Carlos Corredor, Yanlong Pei, Éva Nagy
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	major histocompatibility complex class I fowl adenovirus 9 left end transcription unit inclusion body hepatitis Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/309e263af22149f388a4d12a1ee61834
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spelling	oai:doaj.org-article:309e263af22149f388a4d12a1ee618342021-11-25T19:13:22ZDownregulation of Cell Surface Major Histocompatibility Complex Class I Expression Is Mediated by the Left-End Transcription Unit of Fowl Adenovirus 910.3390/v131122111999-4915https://doaj.org/article/309e263af22149f388a4d12a1ee618342021-11-01T00:00:00Zhttps://www.mdpi.com/1999-4915/13/11/2211https://doaj.org/toc/1999-4915Major histocompatibility complex class I (MHC-I) molecules play a critical role in the host’s antiviral response by presenting virus-derived antigenic peptides to cytotoxic T lymphocytes (CTLs), enabling the clearance of virus-infected cells. Human adenoviruses evade CTL-mediated cell lysis, in part, by interfering directly with the MHC-I antigen presentation pathway through the expression of E3-19K, which binds both MHC-I and the transporter associated with antigen processing protein and sequestering MHC-I within the endoplasmic reticulum. Fowl adenoviruses have no homologues of E3-19K. Here, we show that representative virus isolates of the species <i>Fowl aviadenovirus C</i>, <i>Fowl aviadenovirus D</i>, and <i>Fowl aviadenovirus E</i> downregulate the cell surface expression of MHC-I in chicken hepatoma cells, resulting in 71%, 11%, and 14% of the baseline expression level, respectively, at 12 h post-infection. Furthermore, this work reports that FAdV-9 downregulates cell surface MHC-I through a minimum of two separate mechanisms—a lysosomal-independent mechanism that requires the presence of the fowl adenovirus early 1 (FE1) transcription unit located within the left terminal genomic region between nts 1 and 6131 and a lysosomal-dependent mechanism that does not require the presence of FE1. These results establish a new functional role for the FE1 transcription unit in immune evasion. These studies provide important new information about the immune evasion of FAdVs and will enhance our understanding of the pathogenesis of inclusion body hepatitis and advance the progress made in next-generation FAdV-based vectors.Bryan D. GriffinJuan Carlos CorredorYanlong PeiÉva NagyMDPI AGarticlemajor histocompatibility complex class Ifowl adenovirus 9left end transcription unitinclusion body hepatitisMicrobiologyQR1-502ENViruses, Vol 13, Iss 2211, p 2211 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	major histocompatibility complex class I fowl adenovirus 9 left end transcription unit inclusion body hepatitis Microbiology QR1-502
spellingShingle	major histocompatibility complex class I fowl adenovirus 9 left end transcription unit inclusion body hepatitis Microbiology QR1-502 Bryan D. Griffin Juan Carlos Corredor Yanlong Pei Éva Nagy Downregulation of Cell Surface Major Histocompatibility Complex Class I Expression Is Mediated by the Left-End Transcription Unit of Fowl Adenovirus 9
description	Major histocompatibility complex class I (MHC-I) molecules play a critical role in the host’s antiviral response by presenting virus-derived antigenic peptides to cytotoxic T lymphocytes (CTLs), enabling the clearance of virus-infected cells. Human adenoviruses evade CTL-mediated cell lysis, in part, by interfering directly with the MHC-I antigen presentation pathway through the expression of E3-19K, which binds both MHC-I and the transporter associated with antigen processing protein and sequestering MHC-I within the endoplasmic reticulum. Fowl adenoviruses have no homologues of E3-19K. Here, we show that representative virus isolates of the species <i>Fowl aviadenovirus C</i>, <i>Fowl aviadenovirus D</i>, and <i>Fowl aviadenovirus E</i> downregulate the cell surface expression of MHC-I in chicken hepatoma cells, resulting in 71%, 11%, and 14% of the baseline expression level, respectively, at 12 h post-infection. Furthermore, this work reports that FAdV-9 downregulates cell surface MHC-I through a minimum of two separate mechanisms—a lysosomal-independent mechanism that requires the presence of the fowl adenovirus early 1 (FE1) transcription unit located within the left terminal genomic region between nts 1 and 6131 and a lysosomal-dependent mechanism that does not require the presence of FE1. These results establish a new functional role for the FE1 transcription unit in immune evasion. These studies provide important new information about the immune evasion of FAdVs and will enhance our understanding of the pathogenesis of inclusion body hepatitis and advance the progress made in next-generation FAdV-based vectors.
format	article
author	Bryan D. Griffin Juan Carlos Corredor Yanlong Pei Éva Nagy
author_facet	Bryan D. Griffin Juan Carlos Corredor Yanlong Pei Éva Nagy
author_sort	Bryan D. Griffin
title	Downregulation of Cell Surface Major Histocompatibility Complex Class I Expression Is Mediated by the Left-End Transcription Unit of Fowl Adenovirus 9
title_short	Downregulation of Cell Surface Major Histocompatibility Complex Class I Expression Is Mediated by the Left-End Transcription Unit of Fowl Adenovirus 9
title_full	Downregulation of Cell Surface Major Histocompatibility Complex Class I Expression Is Mediated by the Left-End Transcription Unit of Fowl Adenovirus 9
title_fullStr	Downregulation of Cell Surface Major Histocompatibility Complex Class I Expression Is Mediated by the Left-End Transcription Unit of Fowl Adenovirus 9
title_full_unstemmed	Downregulation of Cell Surface Major Histocompatibility Complex Class I Expression Is Mediated by the Left-End Transcription Unit of Fowl Adenovirus 9
title_sort	downregulation of cell surface major histocompatibility complex class i expression is mediated by the left-end transcription unit of fowl adenovirus 9
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/309e263af22149f388a4d12a1ee61834
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Downregulation of Cell Surface Major Histocompatibility Complex Class I Expression Is Mediated by the Left-End Transcription Unit of Fowl Adenovirus 9

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