scholarly journals Modulation of Endosome Function, Vesicle Trafficking and Autophagy by Human Herpesviruses

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 542
Author(s):  
Eduardo I. Tognarelli ◽  
Antonia Reyes ◽  
Nicolás Corrales ◽  
Leandro J. Carreño ◽  
Susan M. Bueno ◽  
...  
Keyword(s):  
Membrane Trafficking ◽  
Viral Gene ◽  
Barr Virus ◽  
Cellular Processes ◽  
Antiviral Therapies ◽  
Host Determinants ◽  
Viral Particles ◽  
Life Threatening ◽  
Epstein Barr ◽  
Human Herpesviruses

Human herpesviruses are a ubiquitous family of viruses that infect individuals of all ages and are present at a high prevalence worldwide. Herpesviruses are responsible for a broad spectrum of diseases, ranging from skin and mucosal lesions to blindness and life-threatening encephalitis, and some of them, such as Kaposi’s sarcoma-associated herpesvirus (KSHV) and Epstein–Barr virus (EBV), are known to be oncogenic. Furthermore, recent studies suggest that some herpesviruses may be associated with developing neurodegenerative diseases. These viruses can establish lifelong infections in the host and remain in a latent state with periodic reactivations. To achieve infection and yield new infectious viral particles, these viruses require and interact with molecular host determinants for supporting their replication and spread. Important sets of cellular factors involved in the lifecycle of herpesviruses are those participating in intracellular membrane trafficking pathways, as well as autophagic-based organelle recycling processes. These cellular processes are required by these viruses for cell entry and exit steps. Here, we review and discuss recent findings related to how herpesviruses exploit vesicular trafficking and autophagy components by using both host and viral gene products to promote the import and export of infectious viral particles from and to the extracellular environment. Understanding how herpesviruses modulate autophagy, endolysosomal and secretory pathways, as well as other prominent trafficking vesicles within the cell, could enable the engineering of novel antiviral therapies to treat these viruses and counteract their negative health effects.

Herpesviruses (excluding Epstein–Barr virus)

2020 ◽  
pp. 734-754
Author(s):  
J.G.P. Sissons
Keyword(s):  
Primary Infection ◽  
Biological Properties ◽  
Serological Testing ◽  
Barr Virus ◽  
Double Stranded Dna ◽  
Viral Particles ◽  
Immunosuppressed Patients ◽  
Polymerase Chain ◽  
Epstein Barr ◽  
Human Herpesviruses

The Herpesviridae family is widely distributed in the animal kingdom. More than 100 have been isolated from humans, primates, and other mammals, and from reptiles and fish. Eight human herpesviruses, all with a linear double-stranded DNA genome and divided into alpha-, beta-, and gamma-subfamilies on the basis of genomic and biological properties, share the capacity to produce latent infection. The diseases they cause may result from primary infection, or reactivation of the virus from latency, and tend to be more severe in immunosuppressed patients. Diagnosis of the various herpesvirus infections may be made on clinical grounds alone, by culture or demonstration of viral particles by electron microscopy of relevant samples, by serological testing, or now more routinely by polymerase chain reaction-based tests.

Herpesviruses (excluding Epstein–Barr virus)

2010 ◽  
pp. 482-501
Author(s):  
J.G.P. Sissons
Keyword(s):  
Primary Infection ◽  
Biological Properties ◽  
Serological Testing ◽  
Barr Virus ◽  
Double Stranded Dna ◽  
Viral Particles ◽  
Immunosuppressed Patients ◽  
Alpha Beta ◽  
Epstein Barr ◽  
Human Herpesviruses

Eight human herpesviruses, all with a linear double-stranded DNA genome and divided into alpha-, beta-, and gamma-subfamilies on the basis of genomic and biological properties, share the capacity to produce latent infection. The diseases they cause may result from primary infection, or reactivation of the virus from latency, and tend to be more severe in immunosuppressed patients. Diagnosis of the various herpesvirus infections may be made on clinical grounds alone, by culture or demonstration of viral particles by electron microscopy of relevant samples, by serological testing, or (increasingly) by PCR-based tests....

scholarly journals Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: The Human Herpesviruses Are Back!

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 185
Author(s):  
Maria Eugenia Ariza
Keyword(s):  
Chronic Fatigue Syndrome ◽  
Disease Process ◽  
Chronic Fatigue ◽  
Myalgic Encephalomyelitis ◽  
Barr Virus ◽  
Fatigue Syndrome ◽  
Specific Proteins ◽  
Epstein Barr ◽  
Human Herpesviruses

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) or Systemic Exertion Intolerance Disease (SEID) is a chronic multisystem illness of unconfirmed etiology. There are currently no biomarkers and/or signatures available to assist in the diagnosis of the syndrome and while numerous mechanisms have been hypothesized to explain the pathology of ME/CFS, the triggers and/or drivers remain unknown. Initial studies suggested a potential role of the human herpesviruses especially Epstein-Barr virus (EBV) in the disease process but inconsistent and conflicting data led to the erroneous suggestion that these viruses had no role in the syndrome. New studies using more advanced approaches have now demonstrated that specific proteins encoded by EBV could contribute to the immune and neurological abnormalities exhibited by a subgroup of patients with ME/CFS. Elucidating the role of these herpesvirus proteins in ME/CFS may lead to the identification of specific biomarkers and the development of novel therapeutics.

scholarly journals Human Herpesvirus and the Immune Checkpoint PD-1/PD-L1 Pathway: Disorders and Strategies for Survival

2021 ◽  
Vol 9 (4) ◽  
pp. 778
Author(s):  
Takayuki Murata
Keyword(s):  
Cell Death ◽  
Immune System ◽  
Programmed Cell Death ◽  
Immune Checkpoint ◽  
Human Herpesvirus ◽  
Barr Virus ◽  
Programmed Cell Death 1 ◽  
Epstein Barr ◽  
Simplex Virus ◽  
Human Herpesviruses

The immune system has evolved as a complex and efficient means of coping with extrinsic materials, such as pathogens and toxins, as well as intrinsic abnormalities, such as cancers. Although rapid and timely activation of the immune system is obviously important, regulated downregulation of the system is almost as significant as activation to prevent runaway immunity, such as allergies and hypercytokinemia. Therefore, the immune checkpoint programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway is beneficial for the host. On the other hand, pathogens have evolved to evade host immunity by taking advantage of the PD-1/PD-L1 pathway. This review is focused on human herpesviruses, such as herpes simplex virus (HSV), cytomegalovirus (CMV), and Epstein–Barr virus (EBV), which cause various types of disorders, and their relationships with the PD-1/PD-L1 pathway. Understanding such relationships will be useful for developing preventative and therapeutic methods for disorders caused by herpesviruses.

scholarly journals The Epstein-Barr Virus Protein Kinase BGLF4 and the Exonuclease BGLF5 Have Opposite Effects on the Regulation of Viral Protein Production

2009 ◽  
Vol 83 (21) ◽  
pp. 10877-10891 ◽  
Author(s):  
Regina Feederle ◽  
Anja M. Mehl-Lautscham ◽  
Helmut Bannert ◽  
Henri-Jacques Delecluse
Keyword(s):  
Protein Kinase ◽  
Viral Protein ◽  
Epstein Barr Virus ◽  
Protein Production ◽  
Opposite Effect ◽  
Viral Gene ◽  
Virus Protein ◽  
Barr Virus ◽  
Viral Genes ◽  
Epstein Barr

ABSTRACT The Epstein-Barr virus BGLF4 and BGLF5 genes encode a protein kinase and an alkaline exonuclease, respectively. Both proteins were previously found to regulate multiple steps of virus replication, including lytic DNA replication and primary egress. However, while inactivation of BGLF4 led to the downregulation of several viral proteins, the absence of BGLF5 had the opposite effect. Using recombinant viruses that lack both viral enzymes, we confirm and extend these initial observations, e.g., by showing that both BGLF4 and BGLF5 are required for proper phosphorylation of the DNA polymerase processivity factor BMRF1. We further found that neither BGLF4 nor BGLF5 is required for baseline viral protein production. Complementation with BGLF5 downregulated mRNA levels and translation of numerous viral genes, though to various degrees, whereas BGLF4 had the opposite effect. BGLF4 and BGLF5 influences on viral expression were most pronounced for BFRF1 and BFLF2, two proteins essential for nuclear egress. For most viral genes studied, cotransfection of BGLF4 and BGLF5 had only a marginal influence on their expression patterns, showing that BGLF4 antagonizes BGLF5-mediated viral gene shutoff. To be able to exert its functions on viral gene expression, BGLF4 must be able to escape BGLF5's shutoff activities. Indeed, we found that BGLF5 stimulated the BGLF4 gene's transcription through an as yet uncharacterized molecular mechanism. The BGLF4/BGLF5 enzyme pair builds a regulatory loop that allows fine-tuning of virus protein production, which is required for efficient viral replication.

scholarly journals Life-threatening Epstein–Barr virus (EBV)-related hepatitis in a renal transplant patient

2020 ◽  
Vol 20 (Suppl 2) ◽  
pp. s38-s38
Author(s):  
Faisal Rehman ◽  
Yahya Makkeyah ◽  
Abdul-Aema Buraq ◽  
Georgina Aldous ◽  
Sohail Ahmad
Keyword(s):  
Renal Transplant ◽  
Epstein Barr Virus ◽  
Renal Transplant Patient ◽  
Transplant Patient ◽  
Barr Virus ◽  
Life Threatening ◽  
Epstein Barr

Complete Heart Block in Epstein-Barr Myocarditis

PEDIATRICS ◽  
1978 ◽  
Vol 62 (5) ◽  
pp. 847-849
Author(s):  
Milton J. Reitman ◽  
Heddu J. Zirin ◽  
Charles J. DeAngelis
Keyword(s):  
Infectious Mononucleosis ◽  
Heart Block ◽  
Epstein Barr Virus ◽  
Complete Heart Block ◽  
Conduction System ◽  
Pacemaker Therapy ◽  
Barr Virus ◽  
Cardiac Evaluation ◽  
Life Threatening ◽  
Epstein Barr

The clinician must recognize that the Epstein-Barr virus can affect the conduction system of the heart. Therefore, children with infectious mononucleosis who develop bradycardia or hypotension deserve careful cardiac evaluation, including serial ECGs. Pacemaker therapy may be necessary in the treatment of life-threatening bradyarrhymias.

scholarly journals Cytomegalovirus and Epstein–Barr Virus Associations with Neurological Diseases and the Need for Vaccine Development

Vaccines ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 35 ◽  
Author(s):  
Peter A. C. Maple
Keyword(s):  
Infectious Mononucleosis ◽  
Epstein Barr Virus ◽  
Vaccine Development ◽  
Neurological Diseases ◽  
Human Herpesvirus ◽  
Middle Income ◽  
Barr Virus ◽  
Wide Range ◽  
Epstein Barr ◽  
Human Herpesviruses

Herpesviruses have been isolated from a wide range of hosts including humans—for which, nine species have been designated. The human herpesviruses are highly host adapted and possess the capacity for latency, allowing them to survive in the host for life, effectively hidden from the immune system. This ability of human herpesviruses to modulate the host immune response poses particular challenges for vaccine development but at the same time proves attractive for the application of human herpesvirus vaccines to certain spheres of medicine. In this review, congenital cytomegalovirus (CMV) infection and hearing loss will be described followed by a comment on the status of current vaccine development. Secondly, the association of Epstein–Barr virus (EBV) infection with multiple sclerosis (MS) and how EBV vaccination may be of benefit will then be discussed. Prevention of congenital CMV by vaccination is an attractive proposition and several vaccines have been evaluated for potential use. Particularly challenging for the development of CMV vaccines are the needs to prevent primary infection, reinfection, and reactivation at the same time as overcoming the capacity of the virus to generate highly sophisticated immunomodulatory mechanisms. Cost and the practicalities of administering potential vaccines are also significant issues, particularly for low- and middle-income countries, where the burden of disease is greatest. An effective EBV vaccine that could prevent the 200,000 new EBV-associated malignancies which occur globally each year is not currently available. There is increasing interest in developing EBV vaccines to prevent MS and, in view of the association of infectious mononucleosis with MS, reducing childhood infectious mononucleosis is a potential intervention. Currently, there is no licensed EBV vaccine and, in order to progress the development of EBV vaccines for preventing MS, a greater understanding of the association of EBV with MS is required.

scholarly journals Nivolumab treatment of relapsed/refractory Epstein-Barr virus–associated hemophagocytic lymphohistiocytosis in adults

Blood ◽  
2020 ◽  
Vol 135 (11) ◽  
pp. 826-833 ◽  
Author(s):  
Pengpeng Liu ◽  
Xiangyu Pan ◽  
Chong Chen ◽  
Ting Niu ◽  
Xiao Shuai ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Epstein Barr Virus ◽  
Sequencing Analysis ◽  
Hematopoietic Stem ◽  
Barr Virus ◽  
Life Threatening ◽  
Programmed Death Protein 1 ◽  
Epstein Barr

Abstract Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (EBV-HLH) is a life-threatening hyperinflammatory syndrome triggered by EBV infection. It often becomes relapsed or refractory (r/r), given that etoposide-based regimens cannot effectively clear the virus. r/r EBV-HLH is invariably lethal in adults without allogeneic hematopoietic stem cell transplantation. Here, we performed a retrospective analysis of 7 r/r EBV-HLH patients who were treated with nivolumab on a compassionate-use basis at West China Hospital. All 7 patients tolerated the treatment and 6 responded to it. Five of them achieved and remained in clinical complete remission with a median follow-up of 16 months (range, 11.4-18.9 months). Importantly, both plasma and cellular EBV-DNAs were completely eradicated in 4 patients. Single-cell RNA-sequencing analysis showed that HLH syndrome was associated with hyperactive monocytes/macrophages and ineffective CD8 T cells with a defective activation program. Nivolumab treatment expanded programmed death protein-1–positive T cells and restored the expression of HLH-associated degranulation and costimulatory genes in CD8 T cells. Our data suggest that nivolumab, as a monotherapy, provides a potential cure for r/r EBV-HLH, most likely by restoring a defective anti-EBV response.

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