-
Viruses Jul 2017Human herpesvirus-6A (HHV-6A) and human herpesvirus-6B (HHV-6B) are two closely related viruses that infect T-cells. Both HHV-6A and HHV-6B possess telomere-like repeats... (Review)
Review
Human herpesvirus-6A (HHV-6A) and human herpesvirus-6B (HHV-6B) are two closely related viruses that infect T-cells. Both HHV-6A and HHV-6B possess telomere-like repeats at the terminal regions of their genomes that facilitate latency by integration into the host telomeres, rather than by episome formation. In about 1% of the human population, human herpes virus-6 (HHV-6) integration into germline cells allows the viral genome to be passed down from one generation to the other; this condition is called inherited chromosomally integrated HHV-6 (iciHHV-6). This review will cover the history of HHV-6 and recent works that define the biological differences between HHV-6A and HHV-6B. Additionally, HHV-6 integration and inheritance, the capacity for reactivation and superinfection of iciHHV-6 individuals with a second strain of HHV-6, and the role of hypomethylation of human chromosomes during integration are discussed. Overall, the data suggest that integration of HHV-6 in telomeres represent a unique mechanism of viral latency and offers a novel tool to study not only HHV-6 pathogenesis, but also telomere biology. Paradoxically, the integrated viral genome is often defective especially as seen in iciHHV-6 harboring individuals. Finally, gaps in the field of HHV-6 research are presented and future studies are proposed.
Topics: Chromosomes, Human; DNA Methylation; DNA, Viral; Genome, Viral; Herpesvirus 6, Human; Humans; Plasmids; Roseolovirus Infections; Telomere; Virus Activation; Virus Integration; Virus Latency
PubMed: 28737715
DOI: 10.3390/v9070194 -
Microbes and Infection 2018Human cytomegalovirus (HCMV) is the most common cause of viral infection acquired in utero. Even though the infection has been studied for several decades, immune... (Review)
Review
Human cytomegalovirus (HCMV) is the most common cause of viral infection acquired in utero. Even though the infection has been studied for several decades, immune determinants important for virus control and mechanisms of long-term sequelae caused by infection are still insufficiently characterized. Animal models of congenital HCMV infection provide unique opportunity to study various aspects of human disease. In this review, we summarize current knowledge on the role of immune system in congenital CMV infection, with emphasis on lessons learned from mouse model of congenital CMV infection.
Topics: Adaptive Immunity; Animals; Central Nervous System; Cytomegalovirus; Cytomegalovirus Infections; Disease Models, Animal; Humans; Immunity, Innate
PubMed: 29287989
DOI: 10.1016/j.micinf.2017.12.010 -
Current Opinion in Virology Dec 2014The roseoloviruses, human herpesvirus-6A -6B and -7 (HHV-6A, HHV-6B and HHV-7) cause acute infection, establish latency, and in the case of HHV-6A and HHV-6B, whole... (Review)
Review
The roseoloviruses, human herpesvirus-6A -6B and -7 (HHV-6A, HHV-6B and HHV-7) cause acute infection, establish latency, and in the case of HHV-6A and HHV-6B, whole virus can integrate into the host chromosome. Primary infection with HHV-6B occurs in nearly all children and was first linked to the clinical syndrome roseola infantum. However, roseolovirus infection results in a spectrum of clinical disease, ranging from asymptomatic infection to acute febrile illnesses with severe neurologic complications and accounts for a significant portion of healthcare utilization by young children. Recent advances have underscored the association of HHV-6B and HHV-7 primary infection with febrile status epilepticus as well as the role of reactivation of latent infection in encephalitis following cord blood stem cell transplantation.
Topics: Herpesvirus 6, Human; Herpesvirus 7, Human; Humans; Prevalence; Roseolovirus Infections
PubMed: 25462439
DOI: 10.1016/j.coviro.2014.09.013 -
Viruses Feb 2022Cytomegalovirus (CMV) infection of the gastrointestinal (GI) tract can be fatal. However, very few studies have provided comprehensive analyses and specified the...
Cytomegalovirus (CMV) infection of the gastrointestinal (GI) tract can be fatal. However, very few studies have provided comprehensive analyses and specified the differences in symptoms observed in different parts of the GI tract. This study aimed to comprehensively analyze clinical manifestations and management of GI CMV disease. This retrospective cohort study enrolled the patients who had CMV diseases of the GI tract proved by CMV immunohistochemistry stain from the pathology database in a 4000-bed tertiary medical center between January 2000 and May 2021. The patient characteristics, clinical manifestations, endoscopic features, treatments, outcomes, and prognostic factors were analyzed. A total of 356 patients were enrolled, including 46 infected in the esophagus, 76 in the stomach, 30 in the small intestine, and 204 in the colon. In total, 49.4% patients were immunocompromised. The overall in-hospital mortality rate was 20.8%: CMV enteritis had the highest rate (23.3%). Sixty percent of patients received antiviral treatment and 16% were administered both intravenous and oral anti-viral drugs (Combo therapy, minimal and mean treatment duration were 14 and 39.9 ± 25 days). Prognostic factors of in-hospital mortality included age, immune status, albumin level, platelet count, GI bleeding, time-to-diagnosis, and Combo therapy. In the survival analysis, immunocompetent patients receiving Combo therapy had the best survival curve, and immunocompromised patients receiving non-Combo therapy had the worst survival curve. Combo therapy ≥14 days resulted in a better outcome for both immunocompromised and immunocompetent patients. In conclusion, CMV GI diseases affect both immunocompromised and immunocompetent hosts, and a complete treatment course should be considered for patients with poor prognostic factors.
Topics: Adult; Aged; Aged, 80 and over; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Female; Gastrointestinal Diseases; Humans; Immunocompromised Host; Male; Middle Aged; Retrospective Studies
PubMed: 35215942
DOI: 10.3390/v14020352 -
Proceedings of the National Academy of... Jan 2022Transmissible vaccines have the potential to revolutionize how zoonotic pathogens are controlled within wildlife reservoirs. A key challenge that must be overcome is...
Transmissible vaccines have the potential to revolutionize how zoonotic pathogens are controlled within wildlife reservoirs. A key challenge that must be overcome is identifying viral vectors that can rapidly spread immunity through a reservoir population. Because they are broadly distributed taxonomically, species specific, and stable to genetic manipulation, betaherpesviruses are leading candidates for use as transmissible vaccine vectors. Here we evaluate the likely effectiveness of betaherpesvirus-vectored transmissible vaccines by developing and parameterizing a mathematical model using data from captive and free-living mouse populations infected with murine cytomegalovirus (MCMV). Simulations of our parameterized model demonstrate rapid and effective control for a range of pathogens, with pathogen elimination frequently occurring within a year of vaccine introduction. Our results also suggest, however, that the effectiveness of transmissible vaccines may vary across reservoir populations and with respect to the specific vector strain used to construct the vaccine.
Topics: Algorithms; Animal Diseases; Animals; Bayes Theorem; Betaherpesvirinae; Disease Reservoirs; Disease Vectors; Genetic Vectors; Herpesviridae Infections; Immunogenicity, Vaccine; Mice; Models, Theoretical; Muromegalovirus; Nucleic Acid-Based Vaccines; Prevalence; Vaccines
PubMed: 35046024
DOI: 10.1073/pnas.2108610119 -
Medical Microbiology and Immunology Jun 2015In celebrating the 60th anniversary of the first isolation of human cytomegalovirus (HCMV), we reflect on the merits and limitations of the viral strains currently being... (Review)
Review
In celebrating the 60th anniversary of the first isolation of human cytomegalovirus (HCMV), we reflect on the merits and limitations of the viral strains currently being used to develop urgently needed treatments. HCMV research has been dependent for decades on the high-passage strains AD169 and Towne, heavily exploiting their capacity to replicate efficiently in fibroblasts. However, the genetic integrity of these strains is so severely compromised that great caution needs to be exercised when considering their past and future use. It is now evident that wild-type HCMV strains are not readily propagated in vitro. HCMV mutants are rapidly selected during isolation in fibroblasts, reproducibly affecting gene RL13, the UL128 locus (which includes genes UL128, UL130 and UL131A) and often the U(L)/b' region. As a result, the virus becomes less cell associated, altered in tropism and less pathogenic. This problem is not restricted to high-passage strains, as even low-passage strains can harbour biologically significant mutations. Cloning and manipulation of the HCMV genome as a bacterial artificial chromosome (BAC) offers a means of working with stable, genetically defined strains. To this end, the low-passage strain Merlin genome was cloned as a BAC and sequentially repaired to match the viral sequence in the original clinical sample from which Merlin was derived. Restoration of UL128L to wild type was detrimental to growth in fibroblasts, whereas restoration of RL13 impaired growth in all cell types tested. Stable propagation of phenotypically wild-type virus could be achieved only by placing both regions under conditional expression. In addition to the development of these tools, the Merlin transcriptome and proteome have been characterized in unparalleled detail. Although Merlin may be representative of the clinical agent, high-throughput whole-genome deep sequencing studies have highlighted the remarkable high level of interstrain variation present in circulating virus. There is a need to develop systems capable of addressing the significance of this diversity, free from the confounding effects of genetic changes associated with in vitro adaptation. The generation of a set of BAC clones, each containing the genome of a different HCMV strain repaired to match the sequence in the clinical sample, would provide a pathway to address the biological and clinical effects of natural variation in wild-type HCMV.
Topics: Animals; Cytomegalovirus; Cytomegalovirus Infections; Evolution, Molecular; Gene Expression Regulation, Viral; Genes, Viral; Genetic Variation; Genome, Viral; Humans; Mutation; Selection, Genetic; Systems Biology
PubMed: 25894764
DOI: 10.1007/s00430-015-0411-4 -
Molecular Microbiology Jun 2022Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus and the leading cause of congenital disabilities as well as a significant cause of disease in immunocompromised... (Review)
Review
Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus and the leading cause of congenital disabilities as well as a significant cause of disease in immunocompromised patients. The envelopment and egress of HCMV particles is an essential step of the viral life cycle as it determines viral spread and potentially tropism. Here we review the current literature on HCMV envelopment and egress with a particular focus on the role of virus-containing multivesicular body-like vesicles for virus egress and spread. We discuss the difficulties of determining the cellular provenance of these structures in light of viral redistribution of cellular marker proteins and provide potential paths to illuminate their genesis. Finally, we discuss how divergent egress pathways could result in virions of different tropisms.
Topics: Cytomegalovirus; Humans; Proteins; Virion; Virus Assembly
PubMed: 35607767
DOI: 10.1111/mmi.14946 -
Current Opinion in Virology Dec 2014Recent technological advances have led to an explosion in the system-wide profiling of biological processes in the study of herpesvirus biology, herein referred to as... (Review)
Review
Recent technological advances have led to an explosion in the system-wide profiling of biological processes in the study of herpesvirus biology, herein referred to as '-omics'. In many cases these approaches have revealed novel virus-induced changes to host cell biology that can be targeted with new antiviral therapeutics. Despite these successes, -omics approaches are not widely applied in the study of roseoloviruses. Here we describe examples of how -omics studies have shaped our understanding of herpesvirus biology, and discuss how these approaches might be used to identify host and viral factors that mediate roseolovirus pathogenesis.
Topics: Gene Expression Profiling; Genomics; Host-Pathogen Interactions; Humans; Metabolomics; Proteomics; Roseolovirus; Systems Biology; Virology
PubMed: 25437230
DOI: 10.1016/j.coviro.2014.09.021 -
Transplant International : Official... 2023Utilizing assays that assess specific T-cell-mediated immunity against cytomegalovirus (CMV) holds the potential to enhance personalized strategies aimed at preventing... (Review)
Review
Utilizing assays that assess specific T-cell-mediated immunity against cytomegalovirus (CMV) holds the potential to enhance personalized strategies aimed at preventing and treating CMV in organ transplantation. This includes improved risk stratification during transplantation compared to relying solely on CMV serostatus, as well as determining the optimal duration of antiviral prophylaxis, deciding on antiviral therapy when asymptomatic replication occurs, and estimating the risk of recurrence. In this review, we initially provide an overlook of the current concepts into the immune control of CMV after transplantation. We then summarize the existent literature on the clinical experience of the use of immune monitoring in organ transplantation, with a particular interest on the outcomes of interventional trials. Current evidence indicates that cell-mediated immune assays are helpful in identifying patients at low risk for replication for whom preventive measures against CMV can be safely withheld. As more data accumulates from these and other clinical scenarios, it is foreseeable that these assays will likely become part of the routine clinical practice in organ transplantation.
Topics: Humans; Cytomegalovirus; Cytomegalovirus Infections; Antiviral Agents; Immunity, Cellular; Organ Transplantation
PubMed: 38020746
DOI: 10.3389/ti.2023.11963 -
Dermatology (Basel, Switzerland) 2016Pityriasis rosea (PR) is an acute, self-limiting exanthematous disease associated with the endogenous systemic reactivation of human herpesvirus (HHV)-6 and/or HHV-7.... (Review)
Review
Pityriasis rosea (PR) is an acute, self-limiting exanthematous disease associated with the endogenous systemic reactivation of human herpesvirus (HHV)-6 and/or HHV-7. The disease typically begins with a single, erythematous plaque followed by a secondary eruption with lesions on the cleavage lines of the trunk (configuration of a 'Christmas tree'). The duration may vary from 2 weeks to a few months. Besides the typical presentation of PR, atypical forms have been described. The previous classifications of PR are mainly based on its atypical morphological features rather than on the pathogenetic mechanisms that underlie the different presentations of the disease. Notably, most of the morphologically atypical forms follow a course amenable to the classic form. The classification that we propose, taking into account the pathogenesis, clinical features, and course of the disease, is easy and intuitive and may be helpful in identifying the atypical forms of PR in order to avoid misdiagnosis and establish the best treatment options. Finally, this classification provides indications for managing potentially harmful forms of PR (such as PR in pregnancy) and PR-like eruptions.
Topics: Herpesvirus 6, Human; Herpesvirus 7, Human; Humans; Pityriasis Rosea
PubMed: 27096928
DOI: 10.1159/000445375