Deamidation, a type of post-translational modification commonly considered a hallmark of protein“aging” and function decay, is increasingly recognized for its pivotal role in regulating biologicalprocesses and viral...Deamidation, a type of post-translational modification commonly considered a hallmark of protein“aging” and function decay, is increasingly recognized for its pivotal role in regulating biologicalprocesses and viral infection. Our previous study has demonstrated that the deamidation of replicationand transcription activator (RTA), a master regulator of ubiquitous and oncogenic Kaposi's sarcomaassociated herpesvirus (KSHV), mediated by phosphoribosylformylglycinamidine synthetase (PFAS),hinders its nuclear import and transcriptional activity. Here we report that the viral glutamine amidotransferase (vGAT) pseudo-enzyme is exploited to facilitate KSHV lytic infection by inhibiting RTAdeamidation. To be more specific, vGAT interacts with both RTA and cellular PFAS, and inhibits PFASmediated RTA deamidation, thus facilitating RTA nuclear localization and suppressing nuclear factorkappa B (NF-κB) signaling activation, as well as augmenting RTA-mediated transcriptional activationof viral open reading frames (ORFs). In addition, vGAT appears to regulate the deamidation process ofseveral viral ORFs of KSHV. Collectively, these findings unveil that a viral pseudo-enzyme is exploitedto enhance viral infection via deamidation regulation.展开更多
Kaposi’s sarcoma-associated herpesvirus(KSHV), also known as human herpesvirus-8(HHV-8), is etiologically linked to the development of Kaposi’s sarcoma, primary effusion lymphoma, and multicentric Castleman’s disea...Kaposi’s sarcoma-associated herpesvirus(KSHV), also known as human herpesvirus-8(HHV-8), is etiologically linked to the development of Kaposi’s sarcoma, primary effusion lymphoma, and multicentric Castleman’s disease. These malignancies often occur in immunosuppressed individuals, making KSHV infection-associated diseases an increasing global health concern with persistence of the AIDS epidemic. KSHV exhibits biphasic life cycles between latent and lytic infection and extensive transcriptional and posttranscriptional regulation of gene expression. As a member of the herpesvirus family, KSHV has evolved many strategies to evade the host immune response, which help the virus establish a successful lifelong infection. In this review, we summarize the current research status on the biology of latent and lytic viral infection, the regulation of viral life cycles and the related pathogenesis.展开更多
The cell membrane regulates many physiological processes including cellular communication,homing and metabolism. It is therefore not surprising that the composition of the host cell membrane is manipulated by intracel...The cell membrane regulates many physiological processes including cellular communication,homing and metabolism. It is therefore not surprising that the composition of the host cell membrane is manipulated by intracellular pathogens. Among these, the human oncogenic herpesviruses Epstein–Barr virus(EBV) and Kaposi's sarcoma-associated herpesvirus(KSHV)exploit the host cell membrane to avoid immune surveillance and promote viral replication.Accumulating evidence has shown that both EBV and KSHV directly encode several similar membrane-associated proteins, including receptors and receptor-specific ligands(cytokines and chemokines), to increase virus fitness in spite of host antiviral immune responses. These proteins are expressed individually at different phases of the EBV/KSHV life cycle and employ various mechanisms to manipulate the host cell membrane. In recent decades, much effort has been made to address how these membrane-based signals contribute to viral tumorigenesis. In this review, we summarize and highlight the recent understanding of how EBV and KSHV similarly manipulate host cell membrane signals, particularly how remodeling of the cell membrane allows EBV and KSHV to avoid host antiviral immune responses and favors their latent and lytic infection.展开更多
基金funded by the National Natural Science Foundation of China(32173021)the Natural Science Foundation of Hunan Province(2024JJ5184)+2 种基金the Hunan Provincial Science&Technology Major Project(2022sfq30,20231F18)the Key Projects of Hunan Provincial Education Department(23A0196)the Earmarked Fund for Hunan Agriculture Research System(HARS-07).
文摘Deamidation, a type of post-translational modification commonly considered a hallmark of protein“aging” and function decay, is increasingly recognized for its pivotal role in regulating biologicalprocesses and viral infection. Our previous study has demonstrated that the deamidation of replicationand transcription activator (RTA), a master regulator of ubiquitous and oncogenic Kaposi's sarcomaassociated herpesvirus (KSHV), mediated by phosphoribosylformylglycinamidine synthetase (PFAS),hinders its nuclear import and transcriptional activity. Here we report that the viral glutamine amidotransferase (vGAT) pseudo-enzyme is exploited to facilitate KSHV lytic infection by inhibiting RTAdeamidation. To be more specific, vGAT interacts with both RTA and cellular PFAS, and inhibits PFASmediated RTA deamidation, thus facilitating RTA nuclear localization and suppressing nuclear factorkappa B (NF-κB) signaling activation, as well as augmenting RTA-mediated transcriptional activationof viral open reading frames (ORFs). In addition, vGAT appears to regulate the deamidation process ofseveral viral ORFs of KSHV. Collectively, these findings unveil that a viral pseudo-enzyme is exploitedto enhance viral infection via deamidation regulation.
基金supported by the National Key R&D Program of China (2016YFA0502100)the Natural Science Foundation for Distinguished Young Scholars (81425017)+1 种基金the National Institutes of Health awarded (7R01AI116442) to K.Lthe Intramural Research Program of NCI/NIH (1ZIASC010357) to ZMZ
文摘Kaposi’s sarcoma-associated herpesvirus(KSHV), also known as human herpesvirus-8(HHV-8), is etiologically linked to the development of Kaposi’s sarcoma, primary effusion lymphoma, and multicentric Castleman’s disease. These malignancies often occur in immunosuppressed individuals, making KSHV infection-associated diseases an increasing global health concern with persistence of the AIDS epidemic. KSHV exhibits biphasic life cycles between latent and lytic infection and extensive transcriptional and posttranscriptional regulation of gene expression. As a member of the herpesvirus family, KSHV has evolved many strategies to evade the host immune response, which help the virus establish a successful lifelong infection. In this review, we summarize the current research status on the biology of latent and lytic viral infection, the regulation of viral life cycles and the related pathogenesis.
基金supported by the National Natural Science Foundation of China(81471930,81402542)the National Basic Research Program of China(973 Program)(2012CB519001)the National Key Research and Development Program of China(2016YFC1200400)
文摘The cell membrane regulates many physiological processes including cellular communication,homing and metabolism. It is therefore not surprising that the composition of the host cell membrane is manipulated by intracellular pathogens. Among these, the human oncogenic herpesviruses Epstein–Barr virus(EBV) and Kaposi's sarcoma-associated herpesvirus(KSHV)exploit the host cell membrane to avoid immune surveillance and promote viral replication.Accumulating evidence has shown that both EBV and KSHV directly encode several similar membrane-associated proteins, including receptors and receptor-specific ligands(cytokines and chemokines), to increase virus fitness in spite of host antiviral immune responses. These proteins are expressed individually at different phases of the EBV/KSHV life cycle and employ various mechanisms to manipulate the host cell membrane. In recent decades, much effort has been made to address how these membrane-based signals contribute to viral tumorigenesis. In this review, we summarize and highlight the recent understanding of how EBV and KSHV similarly manipulate host cell membrane signals, particularly how remodeling of the cell membrane allows EBV and KSHV to avoid host antiviral immune responses and favors their latent and lytic infection.
