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Pediatric Annals Jan 2024Genital ulcers may be located on the vagina, penis, and anorectal or perineal areas and may be infectious or noninfectious. Vaginal ulcers affect patients of all ages... (Review)
Review
Genital ulcers may be located on the vagina, penis, and anorectal or perineal areas and may be infectious or noninfectious. Vaginal ulcers affect patients of all ages and are commonly due to sexually transmitted infections, such as herpes simplex virus, the most common cause of genital ulcers in the United States. Non-sexually transmitted infections, such as Epstein-Barr virus, and other noninfectious causes, such as trauma, medications, and autoimmune disease, rarely can present with genital ulcers. Appropriate history, examination findings, and targeted testing must be used to correctly diagnose and treat vaginal ulcers. .
Topics: Female; Humans; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Ulcer; Vagina; Vulvovaginitis
PubMed: 38194657
DOI: 10.3928/19382359-20231113-03 -
Journal of Virology Jun 2023Kaposi's sarcoma-associated herpesvirus (KSHV) is a double-stranded DNA (dsDNA) gammaherpesvirus with a poorly characterized lytic replication cycle. However, the lytic...
Kaposi's sarcoma-associated herpesvirus (KSHV) is a double-stranded DNA (dsDNA) gammaherpesvirus with a poorly characterized lytic replication cycle. However, the lytic replication cycle of the alpha- and betaherpesviruses are well characterized. During lytic infection of alpha- and betaherpesviruses, the viral genome is replicated as a precursor form, which contains tandem genomes linked via terminal repeats (TRs). One genomic unit of the precursor form is packaged into a capsid and is cleaved at the TR by the terminase complex. While the alpha- and betaherpesvirus terminases are well characterized, the KSHV terminase remains poorly understood. KSHV open reading frame 7 (ORF7), ORF29, and ORF67.5 are presumed to be components of the terminase complex based on their homology to other terminase proteins. We previously reported that ORF7-deficient KSHV formed numerous immature soccer ball-like capsids and failed to cleave the TRs. ORF7 interacted with ORF29 and ORF67.5; however, ORF29 and ORF67.5 did not interact with each other. While these results suggested that ORF7 is important for KSHV terminase function and capsid formation, the function of ORF67.5 was completely unknown. Therefore, to analyze the function of ORF67.5, we constructed ORF67.5-deficient BAC16. ORF67.5-deficient KSHV failed to produce infectious virus and cleave the TRs, and numerous soccer ball-like capsids were observed in ORF67.5-deficient KSHV-harboring cells. Furthermore, ORF67.5 promoted the interaction between ORF7 and ORF29, and ORF29 increased the interaction between ORF67.5 and ORF7. Thus, our data indicated that ORF67.5 functions as a component of the KSHV terminase complex by contributing to TR cleavage, terminase complex formation, capsid formation, and virus production. Although the formation and function of the alpha- and betaherpesvirus terminase complexes are well understood, the Kaposi's sarcoma-associated herpesvirus (KSHV) terminase complex is still largely uncharacterized. This complex presumably contains KSHV open reading frame 7 (ORF7), ORF29, and ORF67.5. We were the first to report the presence of soccer ball-like capsids in ORF7-deficient KSHV-harboring lytic-induced cells. Here, we demonstrated that ORF67.5-deficient KSHV also formed soccer ball-like capsids in lytic-induced cells. Moreover, ORF67.5 was required for terminal repeat (TR) cleavage, infectious virus production, and enhancement of the interaction between ORF7 and ORF29. ORF67.5 has several highly conserved regions among its human herpesviral homologs. These regions were necessary for virus production and for the interaction of ORF67.5 with ORF7, which was supported by the artificial intelligence (AI)-predicted structure model. Importantly, our results provide the first evidence showing that ORF67.5 is essential for terminase complex formation and TR cleavage.
Topics: Humans; Gene Expression Regulation, Viral; Herpesvirus 8, Human; Viral Proteins; Virus Replication
PubMed: 37272800
DOI: 10.1128/jvi.00475-23 -
Cell Reports Jul 2023Kaposi's sarcoma herpesvirus (KSHV) establishes lifelong infection and persists in latently infected B cells. Paradoxically, in vitro B cell infection is inefficient,...
Kaposi's sarcoma herpesvirus (KSHV) establishes lifelong infection and persists in latently infected B cells. Paradoxically, in vitro B cell infection is inefficient, and cells rapidly die, suggesting the absence of necessary factor(s). KSHV epidemiology unexpectedly mirrors that of malaria and certain helminthic infections, while other herpesviruses are ubiquitous. Elevated circulating monocytes are common in these parasitic infections. Here, we show that KSHV infection of monocytes or M-CSF-differentiated (M2) macrophages is highly efficient. Proteomic analyses demonstrate that infection induces macrophage production of B cell chemoattractants and activating factor. We find that KSHV acts with monocytes or M2 macrophages to stimulate B cell survival, proliferation, and plasmablast differentiation. Further, macrophages drive infected plasma cell differentiation and long-term viral latency. In Kenya, where KSHV is endemic, we find elevated monocyte levels in children with malaria. These findings demonstrate a role for mononuclear phagocytes in KSHV B cell latency and suggest that mononuclear phagocyte abundance may underlie KSHV's geographic disparity.
Topics: Child; Humans; Herpesvirus 8, Human; Proteomics; B-Lymphocytes; Macrophages; Monocytes; Virus Latency
PubMed: 37440412
DOI: 10.1016/j.celrep.2023.112767 -
Pathogens (Basel, Switzerland) Apr 2024The hepatitis D virus (HDV) is a compact, enveloped, circular RNA virus that relies on hepatitis B virus (HBV) envelope proteins to initiate a primary infection in... (Review)
Review
The hepatitis D virus (HDV) is a compact, enveloped, circular RNA virus that relies on hepatitis B virus (HBV) envelope proteins to initiate a primary infection in hepatocytes, assemble, and secrete new virions. Globally, HDV infection affects an estimated 12 million to 72 million people, carrying a significantly elevated risk of developing cirrhosis, liver failure, and hepatocellular carcinoma (HCC) compared to an HBV mono-infection. Furthermore, HDV-associated HCC often manifests at a younger age and exhibits more aggressive characteristics. The intricate mechanisms driving the synergistic carcinogenicity of the HDV and HBV are not fully elucidated but are believed to involve chronic inflammation, immune dysregulation, and the direct oncogenic effects of the HDV. Indeed, recent data highlight that the molecular profile of HCC associated with HDV is unique and distinct from that of HBV-induced HCC. However, the question of whether the HDV is an oncogenic virus remains unanswered. In this review, we comprehensively examined several crucial aspects of the HDV, encompassing its epidemiology, molecular biology, immunology, and the associated risks of liver disease progression and HCC development.
PubMed: 38787214
DOI: 10.3390/pathogens13050362 -
Virology Journal Oct 2023Epstein‒Barr virus (EBV) is a DNA virus that belongs to the human B lymphotropic herpesvirus family and is highly prevalent in the human population. Once infected, a... (Review)
Review
Epstein‒Barr virus (EBV) is a DNA virus that belongs to the human B lymphotropic herpesvirus family and is highly prevalent in the human population. Once infected, a host can experience latent infection because EBV evades the immune system, leading to hosts harboring the virus for their lifetime. EBV is associated with many diseases and causes significant challenges to human health. This review first offers a description of the natural history of EBV infection, clarifies the interaction between EBV and the immune system, and finally focuses on several major types of diseases caused by EBV infection.
Topics: Humans; Epstein-Barr Virus Infections; Herpesvirus 4, Human
PubMed: 37784180
DOI: 10.1186/s12985-023-02187-9 -
Biomedicine & Pharmacotherapy =... Sep 2023Oral cancer is a neoplastic disorder of the oral cavities, including the lips, tongue, buccal mucosa, and lower and upper gums. Oral cancer assessment entails a... (Review)
Review
Oral cancer is a neoplastic disorder of the oral cavities, including the lips, tongue, buccal mucosa, and lower and upper gums. Oral cancer assessment entails a multistep process that requires deep knowledge of the molecular networks involved in its progression and development. Preventive measures including public awareness of risk factors and improving public behaviors are necessary, and screening techniques should be encouraged to enable early detection of malignant lesions. Herpes simplex virus (HSV), human papillomavirus (HPV), Epstein-Barr virus (EBV), and Kaposi sarcoma-associated herpesvirus (KSHV) are associated with other premalignant and carcinogenic conditions leading to oral cancer. Oncogenic viruses induce chromosomal rearrangements; activate signal transduction pathways via growth factor receptors, cytoplasmic protein kinases, and DNA binding transcription factors; modulate cell cycle proteins, and inhibit apoptotic pathways. In this review, we present an up-to-date overview on the use of nanomaterials for regulating viral proteins and oral cancer as well as the role of phytocompounds on oral cancer. The targets linking oncoviral proteins and oral carcinogenesis were also discussed.
Topics: Humans; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Retroviridae; Mouth Neoplasms; Risk Factors
PubMed: 37364477
DOI: 10.1016/j.biopha.2023.115035 -
Frontiers in Immunology 2024The development of lymphoma is a complex multistep process that integrates numerous experimental findings and clinical data that have not yet yielded a definitive... (Review)
Review
The development of lymphoma is a complex multistep process that integrates numerous experimental findings and clinical data that have not yet yielded a definitive explanation. Studies of oncogenic viruses can help to deepen insight into the pathogenesis of lymphoma, and identifying associations between lymphoma and viruses that are established and unidentified should lead to cellular and pharmacologically targeted antiviral strategies for treating malignant lymphoma. This review focuses on the pathogenesis of lymphomas associated with hepatitis B and C, Epstein-Barr, and human immunodeficiency viruses as well as Kaposi sarcoma-associated herpesvirus clarify the current status of basic information and recent advances in the development of virus-associated lymphomas.
Topics: Humans; Lymphoma; Oncogenic Viruses; Herpesvirus 8, Human
PubMed: 38482011
DOI: 10.3389/fimmu.2024.1361009 -
Frontiers in Immunology 2024The Epstein-Barr virus (EBV) is a ubiquitous human pathogen linked to various diseases, including infectious mononucleosis and multiple types of cancer. To control and... (Review)
Review
The Epstein-Barr virus (EBV) is a ubiquitous human pathogen linked to various diseases, including infectious mononucleosis and multiple types of cancer. To control and eliminate EBV, the host's immune system deploys its most potent defenses, including pattern recognition receptors, Natural Killer cells, CD8 and CD4 T cells, among others. The interaction between EBV and the human immune system is complex and multifaceted. EBV employs a variety of strategies to evade detection and elimination by both the innate and adaptive immune systems. This demonstrates EBV's mastery of navigating the complexities of the immunological landscape. Further investigation into these complex mechanisms is imperative to advance the development of enhanced therapeutic approaches with heightened efficacy. This review provides a comprehensive overview of various mechanisms known to date, employed by the EBV to elude the immune response, while establishing enduring latent infections or instigate its lytic replication.
Topics: Humans; Herpesvirus 4, Human; Epstein-Barr Virus Infections; Infectious Mononucleosis; T-Lymphocytes; Receptors, Pattern Recognition
PubMed: 38384471
DOI: 10.3389/fimmu.2024.1297994 -
Proceedings of the National Academy of... Aug 2023Autophagy serves as a defense mechanism against intracellular pathogens, but several microorganisms exploit it for their own benefit. Accordingly, certain herpesviruses...
Autophagy serves as a defense mechanism against intracellular pathogens, but several microorganisms exploit it for their own benefit. Accordingly, certain herpesviruses include autophagic membranes into their infectious virus particles. In this study, we analyzed the composition of purified virions of the Epstein-Barr virus (EBV), a common oncogenic γ-herpesvirus. In these, we found several components of the autophagy machinery, including membrane-associated LC3B-II, and numerous viral proteins, such as the capsid assembly proteins BVRF2 and BdRF1. Additionally, we showed that BVRF2 and BdRF1 interact with LC3B-II via their common protein domain. Using an EBV mutant, we identified BVRF2 as essential to assemble mature capsids and produce infectious EBV. However, BdRF1 was sufficient for the release of noninfectious viral envelopes as long as autophagy was not compromised. These data suggest that BVRF2 and BdRF1 are not only important for capsid assembly but together with the LC3B conjugation complex of ATG5-ATG12-ATG15L1 are also critical for EBV envelope release.
Topics: Humans; Capsid; Herpesvirus 4, Human; Viral Envelope; Epstein-Barr Virus Infections; Capsid Proteins
PubMed: 37579175
DOI: 10.1073/pnas.2211281120 -
Nature Communications Aug 2023The recent emergence of a causal link between Epstein-Barr virus (EBV) and multiple sclerosis has generated considerable interest in the development of an effective...
The recent emergence of a causal link between Epstein-Barr virus (EBV) and multiple sclerosis has generated considerable interest in the development of an effective vaccine against EBV. Here we describe a vaccine formulation based on a lymph node targeting Amphiphile vaccine adjuvant, Amphiphile-CpG, admixed with EBV gp350 glycoprotein and an engineered EBV polyepitope protein that includes 20 CD8 T cell epitopes from EBV latent and lytic antigens. Potent gp350-specific IgG responses are induced in mice with titers >100,000 in Amphiphile-CpG vaccinated mice. Immunization including Amphiphile-CpG also induces high frequencies of polyfunctional gp350-specific CD4 T cells and EBV-specific CD8 T cells that are 2-fold greater than soluble CpG and are maintained for >7 months post immunization. This combination of broad humoral and cellular immunity against multiple viral determinants is likely to provide better protection against primary infection and control of latently infected B cells leading to protection against the development of EBV-associated diseases.
Topics: Mice; Animals; Herpesvirus 4, Human; Epstein-Barr Virus Infections; CD8-Positive T-Lymphocytes; Epitopes, T-Lymphocyte; Lymph Nodes; Vaccines, Subunit
PubMed: 37553346
DOI: 10.1038/s41467-023-39770-1