Regulation of the MIE Locus During HCMV Latency and Reactivation

Dooley, Abigail L.; O’Connor, Christine M.

doi:10.3390/pathogens9110869

Cited by 33 publications

(45 citation statements)

References 285 publications

(382 reference statements)

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“…Brie y, after the virus envelope fuses with the plasma membrane of the host cell, the enveloped virus particles are released into the cytoplasm, enter the nucleus through the nuclear pore within a few minutes and release viral DNA triggering the different phases of gene expression. Dooley et al [17] reported that after HCMV infection, through the combined action of chromatin remodeling and transcription factors, the genes expressed in the MIE phase play an important regulatory role in the balance between latent infection and lytic infection. This molecular switch involves the action of a large number of host and viral proteins.…”

Section: Discussionmentioning

confidence: 99%

Expression of Five Target Proteins Related to Human Cytomegalovirus Infection in Brain Metastases of Lung Cancer

Zhao

et al. 2021

Preprint

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Background: The links between brain metastases of lung cancer and human cytomegalovirus (HCMV) infection have been controversial for a long time. This study aims to explore the links between brain metastases of lung cancer and HCMV infection from the perspective of expression and detection of HCMV immediate early gene (IE), guanine nucleotide-binding protein 4 (GBP4), CXC chemokine receptor 4 (CXCR4), thyroid transcription factor 1 (TTF1) and epidermal growth factor receptor (EGFR) proteins. Methods: We collected brain metastases specimens and lung primary tumor specimens of a series of patients that have not undergone any treatment. Conventional hematoxylin and eosin staining and immunohistochemical staining of target molecules was performed. We used the ImageJ software to process the average optical density value of immune complexes and GraphPad Prism 8.0.1 to perform image analysis, and the SPSS 22.0 statistics package (t test) to analyze the expression differences of target molecules.Results: Based on five cases of brain metastases and two cases of lung primary tumors, a total of seven samples were investigated. Conventional pathology diagnosis reported four cases of brain metastases of lung adenocarcinoma and one case of brain metastases of mixed small cell lung cancer with adenocarcinoma. Among the 19 molecular immunopathological test samples, only GBP4, related to HCMV infection, and TTF1, related to metastases, were highly expressed in all seven samples. A comparison of the AOD values of the primary lung cancer to the AOD values of brain metastases, yielded statistically significant differences as follows: in Case No.1, GBP4 (p=0.016), EGRF (p<0.001); in Case No. 2, IE (p<0.001), CXCR4 (p=0.005), EGFR (p=0.023), TTF1 (p=0.004). Conclusions: Although TTF1 is known to be a kinesin for brain metastases of lung cancer cells and it is associated with poor survival prognosis, the role of GBP4, which is closely related to HCMV infection and a key protein of brain metastases of lung cancer, remains unknown. The findings provide new knowledge into the role of GBP4 and could provide clues for devising novel strategies for target molecular therapy research in brain metastases of lung cancer in the context of HCMV infection.

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Section: Discussionmentioning

confidence: 99%

Expression of Five Target Proteins Related to Human Cytomegalovirus Infection in Brain Metastases of Lung Cancer

Zhao

et al. 2021

Preprint

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“…It is also not known whether different sites of myeloid latency (e.g., CD34+ progenitor cells and their derivative CD14+ monocytes) have different latency-associated gene expression signatures. Crucially, in both cell types, the major immediate early promoter/enhancer (MIEP) remains suppressed during latency [ 78 , 79 ]. During latency, viral DNA replication does not occur, and many viral antigens are not expressed.…”

Section: Strategies For Targeting the Latent Hcmv Reservoirmentioning

confidence: 99%

“…A combination of viral and cellular factors are known to act to modulate the transcriptional activity of the MIE locus [ 94 , 95 , 96 ], for reviews see [ 79 , 97 , 98 ]. One such cellular factor is the histone deacetylase HDAC4, which is upregulated in latently infected cells and associates with the MIEP, deacetylating histones to aid in its repression [ 99 ].…”

Section: Strategies For Targeting the Latent Hcmv Reservoirmentioning

confidence: 99%

HCMV Antivirals and Strategies to Target the Latent Reservoir

Perera

Wills

Sinclair

2021

Viruses

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Human cytomegalovirus (HCMV) is a ubiquitous human herpesvirus. In healthy people, primary infection is generally asymptomatic, and the virus can go on to establish lifelong latency in cells of the myeloid lineage. However, HCMV often causes severe disease in the immunosuppressed: transplant recipients and people living with AIDS, and also in the immunonaive foetus. At present, there are several antiviral drugs licensed to control HCMV disease. However, these are all faced with problems of poor bioavailability, toxicity and rapidly emerging viral resistance. Furthermore, none of them are capable of fully clearing the virus from the host, as they do not target latent infection. Consequently, reactivation from latency is a significant source of disease, and there remains an unmet need for treatments that also target latent infection. This review briefly summarises the most common HCMV antivirals used in clinic at present and discusses current research into targeting the latent HCMV reservoir.

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“…HCMV is a human beta-herpesvirus that causes lifelong infection in the host and has been involved in the development of several diseases in humans, generating severe complications in immunocompromised individuals [ 64 , 65 ]. At various micromolar concentrations, the anti-HCMV activity of curcumin was explored in vitro, in an animal model (Balb/c mice) and in silico experiments.…”

Section: Role Of Curcumin In Inhibition Of Various Herpesviruses Imentioning

confidence: 99%

Nutraceutical Curcumin with Promising Protection against Herpesvirus Infections and Their Associated Inflammation: Mechanisms and Pathways

Šudomová¹,

Hassan

2021

Microorganisms

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Herpesviruses are DNA viruses that infect humans and animals with the ability to induce latent and lytic infections in their hosts, causing critical health complications. The enrolment of nutraceutical anti-herpesvirus drugs in clinical investigations with promising levels of reduced resistance, free or minimal cellular toxicity, and diverse mechanisms of action might be an effective way to defeat challenges that hurdle the progress of anti-herpesvirus drug development, including the problems with drug resistance and recurrent infections. Therefore, in this review, we aim to hunt down all investigations that feature the curative properties of curcumin, a principal bioactive phenolic compound of the spice turmeric, in regard to various human and animal herpesvirus infections and inflammation connected with these diseases. Curcumin was explored with potent antiherpetic actions against herpes simplex virus type 1 and type 2, human cytomegalovirus, Kaposi’s sarcoma-associated herpesvirus, Epstein–Barr virus, bovine herpesvirus 1, and pseudorabies virus. The mechanisms and pathways by which curcumin inhibits anti-herpesvirus activities by targeting multiple steps in herpesvirus life/infectious cycle are emphasized. Improved strategies to overcome bioavailability challenges that limit its use in clinical practice, along with approaches and new directions to enhance the anti-herpesvirus efficacy of this compound, are also reviewed. According to the reviewed studies, this paper presents curcumin as a promising natural drug for the prevention and treatment of herpesvirus infections and their associated inflammatory diseases.

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Regulation of the MIE Locus During HCMV Latency and Reactivation

Cited by 33 publications

References 285 publications

Expression of Five Target Proteins Related to Human Cytomegalovirus Infection in Brain Metastases of Lung Cancer

Expression of Five Target Proteins Related to Human Cytomegalovirus Infection in Brain Metastases of Lung Cancer

HCMV Antivirals and Strategies to Target the Latent Reservoir

Nutraceutical Curcumin with Promising Protection against Herpesvirus Infections and Their Associated Inflammation: Mechanisms and Pathways

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