Recent Advances in Developing Treatments of Kaposi's Sarcoma Herpesvirus-Related Diseases.

Kaposi-sarcoma-associated herpesvirus (KSHV) or human herpesvirus 8 (HHV-8) is the causative agent of several malignancies, including Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman's disease (MCD). Active KSHV replication has also been associated with a pathological condition called KSHV inflammatory cytokine syndrome (KICS), and KSHV may play a role in rare cases of post-transplant polyclonal lymphoproliferative disorders. Several commonly used herpesviral DNA polymerase inhibitors are active against KSHV in tissue culture. Unfortunately, they are not always efficacious against KSHV-induced diseases. To improve the outcome for the patients, new therapeutics need to be developed, including treatment strategies that target either viral proteins or cellular pathways involved in tumor growth and/or supporting the viral life cycle. In this review, we summarize the most commonly established treatments against KSHV-related diseases and review recent developments and promising new compounds that are currently under investigation or on the way to clinical use.

Molecular Detection of Human Herpes Viruses in Suspected Measles Serum Samples from Senegal, 2014 to 2017.

Herpesviruses are known to cause a diversity of clinical syndromes, ranging from minor cutaneous lesions to life-threatening illnesses, especially in immunocompromised hosts. Here, we investigate retrospectively the contribution of five human herpesviruses, including herpes simplex virus Cytomegalovirus (CMV), the Epstein-Barr virus (EBV), human herpesvirus 6, and varicella zoster virus (VZV) in serum samples collected from measles suspected patients with at least fever and rash. Sera specimens were first tested for serological evidence of measles and rubella virus infection by ELISA, and DNA extracted from an aliquot of each clinical specimen for molecular detection of human herpes viruses by RT-qPCR. A total of 3,358 specimens have been collected and tested for herpes viruses. Nearly half of the overall suspected cases were children younger than 5 years (49.4%). Of the 3,358 sera tested by ELISA, 227 (6.7%) were measles laboratory confirmed and 152 (4.5%) rubella laboratory confirmed. Herpes viruses were detected in 1763 (52.5%), and VZV was the most common with 44.3%, followed by EBV with 10.7%. Coinfections were found in 352 (20%) cases, and the most common co-detections were VZV/EBV or VZV/CMV (169 and 81 cases, respectively). A clear seasonal pattern of VZV, EBV, and CMV identification was observed, with the highest incidence between February and April each year. Results of this investigation provide more insights into cutaneous rash syndrome etiologies in patients sampled in the framework of measles/rubella surveillance in Senegal, which is useful for the guidance of both case definition revision and clinical practice as well as for public health policy.

Epidemiology of Castleman Disease.

Castleman disease is a rare entity, including unicentric Castleman disease (UCD), human herpesvirus-8 plus Castleman disease (HHV-8+MCD), and idiopathic multicentric Castleman disease (iMCD). UCD is the most common at 16 per million person years and occurs at every age. HHV-8+MCD incidence varies widely, mostly affecting human immunodeficiency virus-positive men. iMCD is likely a more heterogeneous disease with an estimated incidence of 5 per million person years. Improved definitions should improve understanding of the epidemiology of Castleman disease and its subtypes.

Chemokines encoded by herpesviruses.

Viruses use diverse strategies to elude the immune system, including copying and repurposing host cytokine and cytokine receptor genes. For herpesviruses, the chemokine system of chemotactic cytokines and receptors is a common source of copied genes. Here, we review the current state of knowledge about herpesvirus-encoded chemokines and discuss their possible roles in viral pathogenesis, as well as their clinical potential as novel anti-inflammatory agents or targets for new antiviral strategies.

New approaches to the treatment of human herpesvirus 8-associated disease.

Human herpesvirus 8 (HHV-8, also known as Kaposi sarcoma-associated herpesvirus or KSHV) is the etiologic agent of Kaposi sarcoma (KS) and primary effusion lymphoma (PEL), as well as many cases of Castleman disease. Despite significant advances in understanding the biology and natural history of these diseases, current treatment options have important limitations, and strategies to prevent their development in high-risk individuals are lacking. This article reviews the scope of HHV-8-associated disease, as well as the efficacy of current treatment options. Finally, novel approaches to treatment and prevention are described, including antiviral agents, targeted molecular therapy and a combination of these modalities.

The expanding spectrum of herpesvirus infections of the nervous system.

Herpesviruses cause various acute, subacute, and chronic disorders of the central (CNS) and peripheral (PNS) nervous systems in adults and children. Both immunocompetent and immunocompromised individuals may be affected. Zoster (shingles), a result of reactivation of varicella zoster virus (VZV), is the most frequent neurologic complication. Other neurological complications include encephalitis produced by type I herpes simplex virus (HSV-1), and less frequently HSV-2, as well as by VZV and cytomegalovirus (CMV). Acute meningitis is seen with VZV and HSV-2, and benign recurrent meningitis with HSV-2. Combinations of meningitis/ encephalitis and myelitis/radiculitis are associated with Epstein Barr Virus (EBV); myelitis with VZV, CMV, EBV, and HSV-2; and ventriculitis/encephalitis with VZV and CMV. Brainstem encephalitis due to HSV and VZV, and polymyeloradiculitis due to CMV are well documented. HHV-6 produces childhood exanthem subitum (roseola) and febrile convulsions. Immunocompetent and immunocompromised hosts manifest different incidences and patterns of herpesvirus infections. For example, stroke due to VZV-mediated large vessel disease (herpes zoster ophthalmicus) occurs predominantly in immunocompetent hosts, while small vessel disease (leukoencephalitis) and ventriculitis develop almost exclusively in immunocompromised patients. EBV-associated primary CNS lymphomas also are restricted to immunosuppressed individuals. Recent large CSF PCR studies have shown that VZV, EBV, and CMV more frequently produce meningitis, encephalitis, or encephalopathy in immunocompetent hosts than was formerly realized. We review herpesvirus infections of the nervous system and illustrate the expanding spectrum of disease by including examples of a 75-year-old male on steroid treatment for chronic lung disease with fatal HSV-2 meningitis and an 81-year-old male with myasthenia gravis, long-term azathioprine use, and an EBV-associated primary CNS lymphoma.

[Etiological diagnosis and classification of Herpes virus-associated disturbances of the central nervous system]. / Etiologichna diagnostyka ta klasyfikatsiia gerpesvirusnykh urazhen' tsentral'noï nervovoï systemy.

An etiological classification is submitted of Herpes virus-induced affections of the central nervous system (CNS), such as monoherpesviral, herpesvirus-bacterial, herpesvirus-spirochetal, herpesvirus-mycotic, herpesvirus-protozoan affections. Excerpts from case records of etiologically confirmed mixed infections are given. Consideration is given to such herpesviruses as HSV, CMV, EBV, VZV. Other possible combinations of etiological agents include herpesvirus + chlamidia, mycoplasms, prions.

[Preoperative classification of malignant stomach tumors]. / Zur Problematik der präoperativen Klassifikation von bösartigen Magentumoren.

Based on the case report of a 51 year-old patient presenting with a lymphoepithelioma like gastric cancer, we discuss the diagnostic challenge to differentiate this entity from gastric non-Hodgkin lymphoma. Since high-level lymphoid stromal reactions are rarely associated with gastric adenocarcinoma, misinterpretation can occur easily. In addition to the lymphoepithelioma like gastric cancer that is often associated with a demonstrable EBV association of the tumor cells, synchronous development of gastric carcinoma and lymphoma must be considered. Establishment of a correct diagnosis requires multiple, deep and multifocally sampled gastric biopsies, and immunohistochemical and molecular techniques to supplement conventional histology. Only through this procedure are correct characterization and classification of these unusual gastric neoplasms possible.

Herpesvirus vaccines. Development, controversies, and applications.

Herpesviruses present difficult challenges in vaccine development because of their ability to evade immune clearance. Data and recommendations regarding the live-attenuated varicella vaccine are discussed. Approaches to developing vaccines to prevent herpes simplex virus (HSV), cytomegalovirus (CMV), and Epstein-Barr virus (EBV)-associated illnesses also are considered.

Infecciones herpéticas / Herpetic infections

Los virus Herpes conforman una vasta familia de virus ADN, que están constituidos por un cápside formado por 162 subunidades o capsómeros, rodeado por una envoltura lipídica con espículas, las que al igual que los capsómeros representan sitios antigénicos que permiten la adhesión del virus a la superficie de las células susceptibles o permisivas a las cuales penetran y en los que se reduplican

Classification of Epstein-Barr virus-associated posttransplant lymphoproliferative diseases: implications for understanding their pathogenesis and developing rational treatment strategies.

The Epstein-Barr virus (EBV) is associated with a spectrum of B-cell lymphoproliferative diseases (LPD) that develop following organ transplantation. A classification scheme for these disorders has been developed based on the clinical, histologic, immunologic cell-typing, cytogenetic, immunoglobulin gene-rearrangement, and virologic characteristics of these LPD. Four disease groups have been identified: (a) uncomplicated posttransplant infectious mononucleosis, (b) benign polyclonal polymorphic B-cell hyperplasia, (c) early malignant transformation in polyclonal polymorphic B-cell lymphoma, and (d) monoclonal polymorphic B-cell lymphoma. This classification has furthered our understanding of the pathogenesis of these diverse LPD and has allowed the development of rational treatment protocols.

Prevalence of human herpesvirus 6 variant A and B infections in bone marrow transplant recipients as determined by polymerase chain reaction and sequence-specific oligonucleotide probe hybridization.

An oligotyping methodology was devised by using the polymerase chain reaction and sequence-specific oligonucleotide probe hybridization in order to discriminate the A and B variants of human herpesvirus 6 (HHV-6). Comparative DNA sequence analysis of portions of the U1102 (variant A) and Z29 (variant B) genomes revealed polymorphic regions which allowed for the synthesis of variant-specific and consensus oligonucleotide probes. These probes were found to hybridize exclusively to their respective HHV-6 variants. This strategy was then further tested by evaluating 16 clinical isolates derived from patients undergoing bone marrow transplantation to determine the subtype prevalence of HHV-6 infection in these patients. All clinical isolates were documented to be of variant B, indicating that the majority of bone marrow transplantation patients may be preferentially infected with this HHV-6 subtype. This oligotyping strategy may be useful in defining the relative prevalence of HHV-6A and HHV-6B infections in patient populations potentially at risk for HHV-6 disease.

Diagnosis of human herpesviruses: memorandum from a WHO meeting.

PIP: The frequent reactivation of disease in immunosuppressed patients represents a serious health complication for acquired immunodeficiency syndrome (AIDS) patients with herpesviruses. Since the herpesviruses are often associated with the development of complication such as pneumonia and lymphoma, an emphasis is being placed on the rapid laboratory diagnosis of herpes simplex viruses 1 and 2, varicella- zoster, Epstein-Barr virus, and cytomegalovirus. Diagnostic methods that utilize monoclonal antibodies to detect viral antigens in clinical specimens are now within the scope of general laboratories and detection methods for viral DNA in clinical specimens are being advanced. Each of the viruses requires its own diagnostic procedures, however, and consideration should be given to practical and economic issues. The World Health Organization (WHO) has recommended that developing countries use rapid diagnostic techniques that do not require expensive, labor-intensive virus replication. Serological diagnosis can facilitate disease surveillance of the herpesviruses in different population groups in countries with little information on this infection's epidemiology. Who is recommending that regional or national reference laboratories establish confirmatory testing facilities to support the routing virological or microbiological services offered by local laboratories. Other WHO recommendations include the development of international standard preparations and reference reagents, compilation of a list of monoclonal antibodies available for collaborative diagnostic studies, and promotion of studies on the rapid diagnosis of herpesvirus-promoted encephalitides.^ieng

[Clinical approach to herpesviruses. A composite overview]. / Approche clinique des herpèsvirus. Un survol synthétique.

This review article describes the lesions due to herpesviruses: herpes simplex, chickenpox, herpes zoster (shingles), and infections due to cytomegalovirus and Epstein-Barr virus. Based on current literature, clinical signs, diagnostic methods and therapeutic possibilities are given for each type of infection. B virus infections of humans are also briefly described.