Lysine residues of interferon regulatory factor 7 affect the replication and transcription activator-mediated lytic replication of Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8

Lysine residues of interferon regulatory factor 7 affect the replication and transcription activator-mediated lytic replication of Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8

Kaposi's sarcoma-associated herpesvirus (KSHV) infection goes through latent and lytic phases, which are controlled by the viral replication and transcription activator (RTA). Upon KSHV infection, the host responds by suppressing RTA-activated lytic gene expression through interferon regulatory...

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Main Authors: Zhang, Tianzheng, Wang, Ying, Zhang, Li, Liu, Bin, Xie, Jinhui, Wood, Charles, Wang, Jinzhong
Format: Online
Language:English
Published: Society for General Microbiology 2011
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052531/
id pubmed-3052531
recordtype oai_dc
spelling pubmed-30525312012-01-01 Lysine residues of interferon regulatory factor 7 affect the replication and transcription activator-mediated lytic replication of Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 Zhang, Tianzheng Wang, Ying Zhang, Li Liu, Bin Xie, Jinhui Wood, Charles Wang, Jinzhong Animal Kaposi's sarcoma-associated herpesvirus (KSHV) infection goes through latent and lytic phases, which are controlled by the viral replication and transcription activator (RTA). Upon KSHV infection, the host responds by suppressing RTA-activated lytic gene expression through interferon regulatory factor 7 (IRF-7), a key regulator of host innate immune response. Lysine residues are potential sites for post-translational modification of IRF-7, and were suggested to be critical for its activity. In this study, we analysed the 15 lysine residues for their effects on IRF-7 function by site-directed mutagenesis. We found that some mutations affect the ability of IRF-7 to activate interferon (IFN)-α1 and IFN-β promoters, to suppress RTA-mediated lytic gene expression and to repress KSHV reactivation and lytic replication. However, other mutations affect only a subset of these four functions. These findings demonstrate that the lysine residues of IRF-7 play important roles in mediating IFN synthesis and modulating viral lytic replication. Society for General Microbiology 2011-01 /pmc/articles/PMC3052531/ /pubmed/20844090 http://dx.doi.org/10.1099/vir.0.021816-0 Text en Copyright © 2011, SGM
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Zhang, Tianzheng
Wang, Ying
Zhang, Li
Liu, Bin
Xie, Jinhui
Wood, Charles
Wang, Jinzhong
spellingShingle Zhang, Tianzheng
Wang, Ying
Zhang, Li
Liu, Bin
Xie, Jinhui
Wood, Charles
Wang, Jinzhong
Lysine residues of interferon regulatory factor 7 affect the replication and transcription activator-mediated lytic replication of Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8
author_facet Zhang, Tianzheng
Wang, Ying
Zhang, Li
Liu, Bin
Xie, Jinhui
Wood, Charles
Wang, Jinzhong
author_sort Zhang, Tianzheng
title Lysine residues of interferon regulatory factor 7 affect the replication and transcription activator-mediated lytic replication of Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8
title_short Lysine residues of interferon regulatory factor 7 affect the replication and transcription activator-mediated lytic replication of Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8
title_full Lysine residues of interferon regulatory factor 7 affect the replication and transcription activator-mediated lytic replication of Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8
title_fullStr Lysine residues of interferon regulatory factor 7 affect the replication and transcription activator-mediated lytic replication of Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8
title_full_unstemmed Lysine residues of interferon regulatory factor 7 affect the replication and transcription activator-mediated lytic replication of Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8
title_sort lysine residues of interferon regulatory factor 7 affect the replication and transcription activator-mediated lytic replication of kaposi's sarcoma-associated herpesvirus/human herpesvirus 8
description Kaposi's sarcoma-associated herpesvirus (KSHV) infection goes through latent and lytic phases, which are controlled by the viral replication and transcription activator (RTA). Upon KSHV infection, the host responds by suppressing RTA-activated lytic gene expression through interferon regulatory factor 7 (IRF-7), a key regulator of host innate immune response. Lysine residues are potential sites for post-translational modification of IRF-7, and were suggested to be critical for its activity. In this study, we analysed the 15 lysine residues for their effects on IRF-7 function by site-directed mutagenesis. We found that some mutations affect the ability of IRF-7 to activate interferon (IFN)-α1 and IFN-β promoters, to suppress RTA-mediated lytic gene expression and to repress KSHV reactivation and lytic replication. However, other mutations affect only a subset of these four functions. These findings demonstrate that the lysine residues of IRF-7 play important roles in mediating IFN synthesis and modulating viral lytic replication.
publisher Society for General Microbiology
publishDate 2011
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052531/
_version_ 1611444085596356608

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