Murine cytomegaloviruses m139 targets DDX3 to curtail interferon production and promote viral replication.

Cytomegaloviruses (CMV) infect many different cell types and tissues in their respective hosts. Monocytes and macrophages play an important role in CMV dissemination from the site of infection to target organs. Moreover, macrophages are specialized in pathogen sensing and respond to infection by secreting cytokines and interferons. In murine cytomegalovirus (MCMV), a model for human cytomegalovirus, several genes required for efficient replication in macrophages have been identified, but their specific functions remain poorly understood. Here we show that MCMV m139, a gene of the conserved US22 gene family, encodes a protein that interacts with the DEAD box helicase DDX3, a protein involved in pathogen sensing and interferon (IFN) induction, and the E3 ubiquitin ligase UBR5. DDX3 and UBR5 also participate in the transcription, processing, and translation of a subset of cellular mRNAs. We show that m139 inhibits DDX3-mediated IFN-α and IFN-ß induction and is necessary for efficient viral replication in bone-marrow derived macrophages. In vivo, m139 is crucial for viral dissemination to local lymph nodes and to the salivary glands. An m139-deficient MCMV also replicated to lower titers in SVEC4-10 endothelial cells. This replication defect was not accompanied by increased IFN-ß transcription, but was rescued by knockout of either DDX3 or UBR5. Moreover, m139 co-localized with DDX3 and UBR5 in viral replication compartments in the cell nucleus. These results suggest that m139 inhibits DDX3-mediated IFN production in macrophages and antagonizes DDX3 and UBR5-dependent functions related to RNA metabolism in endothelial cells.

Kaposi Sarcoma-Associated Herpesvirus and Staphylococcus aureus Coinfection in Oral Cavities of HIV-Positive Patients: A Unique Niche for Oncogenic Virus Lytic Reactivation.

Collectively, viruses are the principal cause of cancers arising in patients with immune dysfunction, including human immunodeficiency virus (HIV)-positive patients. Kaposi sarcoma (KS) etiologically linked to Kaposi sarcoma-associated herpesvirus (KSHV) continues to be the most common AIDS-associated tumor. The involvement of the oral cavity represents one of the most common clinical manifestations of this tumor. HIV infection incurs an increased risk among individuals with periodontal diseases and oral carriage of a variety of pathogenic bacteria. However, whether interactions involving periodontal bacteria and oncogenic viruses in the local environment facilitate replication or maintenance of these viruses in the oral cavity of HIV-positive patients remain largely unknown. We previously showed that pathogen-associated molecular patterns (PAMPs) from specific periodontal bacteria promoted KSHV entry into oral cells and subsequent establishment of latency. In the current study, we demonstrate that Staphylococcus aureus, one of common pathogens causing infection in HIV-positive patients, and its PAMPs can effectively induce KSHV lytic reactivation from infected oral cells, through the Toll-like receptor reactive oxygen species and cyclin D1-Dicer-viral microRNA axis. This investigation provides further clinical evidence about the relevance of coinfection due to these 2 pathogens in the oral cavities of a cohort HIV-positive patients and reveals novel mechanisms through which these coinfecting pathogens potentially promote virus-associated cancer development in the unique niche of immunocompromised patients.

Genetic Diversity of Cyprinid Herpesvirus 3 from Different Geographical Locations during 1999-2019 in the United States of America.

Cyprinid herpesvirus 3, also known as koi herpesvirus (KHV), is an important pathogen in common and koi carp Cyprinus carpio, varieties. Two main genotypes of KHV have been reported worldwide that are associated with Asian and European origins. In the USA, outbreaks of KHV diseases have been reported in different states since the early 1990s; however, the diversity of KHV is unknown. In the current study, 67 DNA samples that were extracted from clinical cases of koi tissues that were submitted for diagnosis during KHV outbreaks from 10 different states in the USA from 1999 to 2019 were used to investigate their genetic diversity. The thymidine kinase gene was amplified, sequenced, and used for phylogenetic analysis. Our results showed that the KHV isolates that were collected from the different states were clustered in the two known KHV genogroups, where 31 isolates belonged to the Asian genotype branch and 36 to the European genotype branch. The spatiotemporal analysis demonstrated fluctuation of KHV genotypes in the USA, as the main KHV genotype that was detected in koi in the USA from 1999 to 2013 was the European genotype, whereas the Asian KHV genotype appeared to emerge in the USA in 2008, increasing in incidence until 2019. The current study provides evidence on the genetic diversity of KHV in the USA. Future studies that evaluate the virulence of these genetically diverse isolates is warranted to obtain a better understanding of the epidemiology of this re-emerging pathogen. This may provide an improved awareness of the current status of KHV and help to control the disease in the koi population in the USA.

Transcriptome analysis reveals an activation of major histocompatibility complex 1 and 2 pathways in chicken trachea immunized with infectious laryngotracheitis virus vaccine.

Infectious laryngotracheitis is an acute, contagious, upper respiratory disease of chickens caused by gallid herpes virus 1. Due to mortality rates that can reach up to 70% depending on the virulence of the virus, the disease is of great economic importance to the poultry industry. In this study, 15-d-old specific pathogen-free White Leghorn chickens were used to perform transcriptome analysis of chicken trachea immunized with infectious laryngotracheitis virus vaccine. Myosin and several collagen-related genes were downregulated in the immunized group, suggesting that normal function and structure may be compromised. In addition, we identified some cytokine receptors and several immune genes, such as Granzyme A (GZMA), CD4 molecule (CD4), CD8a molecule (CD8A), and CD8b molecule (CD8B), that were upregulated upon vaccination. The gene ontology analysis shows that genes included in the biological process cluster were related to antigen processing and presentation, positive regulation of immune system processes, T cell selection, and positive regulation of T cell activation. In conclusion, chicken embryo origin vaccine activation of the major histocompatibility complex 1 and 2 pathways provides insight for evaluation and design of infectious laryngotracheitis vaccines.

[Usefulness of wide-range microbiological diagnostics proceedings in case of simultaneous infection with four herpesviruses after allogeneic haematopoietic stem cell transplantation--a case report]. / Przydatnosc wielokierunkowej diagnostyki mikrobiologicznej na przykladzie jednoczesnego zakazenia czterema herpeswirusami jako powiklania po allogenicznym przeszczepieniu komórek krwiotwórczych--opis przypadku.

INTRODUCTION: Infections caused with a variety of bacteria, fungi and viruses are still responsible for high level of mortality and morbidity in immunosupressed individuals. A case of fatal post-transplant reactivation with four herpesviruses in 49-year-old immunocompromised male with MDS-RAEB2, subjected to allogeneic haematopoietic stem cell transplantation was described. METHODS: Full microbiological examination of was performed in different types of clinical samples (whole blood, stool). Sera specimens were tested for the presence of different viral DNA using the real-time PCR assays. RESULTS AND CONCLUSIONS: DNA of HSV-1, VZV, HHV-6 and EBV in serum samples was detected using molecular biology techniques. Viral level of HSV-1 and VZV was constantly increasing despite routine applied oral acyclovir therapy. These findings underline the value of real-time PCR technique used in current therapeutic procedures and for monitoring of antiviral therapy with nucleoside analogs. We found that real-time PCR is a useful tool in detection and monitoring of disseminated herpesviral infection, especially for the detection of low-copy viraemia in clinical specimens.

Herpesvirus periodontitis: infection beyond biofilm.

Herpesviruses, including Epstein-Barr virus and cytomegalovirus, occur at high copy counts in aggressive periodontitis, and may interact synergistically with periodontopathic bacteria in the etiology of the disease. Herpesvirus active periodontal infections may impair local host defenses and thus increase the aggressiveness of resident periodontopathic bacteria. The bacteria, in turn, may augment the virulence of the herpesviruses. The abundance of herpesviruses in periodontitis redefines the pathogenic paradigm of the disease and may have significant clinical implications.

A systematic review of viral infections associated with oral involvement in cancer patients: a spotlight on Herpesviridea.

PURPOSE: Our aim was to evaluate the literature for the prevalence of and interventions for oral viral infections and, based on scientific evidence, point to effective treatment protocols. Quality of life (QOL) and economic impact were assessed if available in the articles reviewed. METHODS: Our search of the English literature focused on oral viral infections in cancer patients within the timeframe of 1989-2007. Review methods were standardized. Cohort studies were used to determine the weighted prevalence of oral viral infection in cancer patients. The quality of selected articles were assessed and scored with respect to sources of bias, representativeness, scale validity, and sample size. Interventional studies were utilized to determine management guidelines. Literature search included measures of QOL and economic variables. RESULTS: Prevalence of oral herpes simplex virus (HSV) infection in neutropenic patients was higher than in patients treated with radiotherapy for head and neck cancer (49.8% vs. 0%, respectively). In patients treated with radiochemotherapy for head and neck cancer, the prevalence of oral HSV infection increases up to 43.2% (CI, 0-100%). Prevalence of HSV infection was higher when oral ulcers existed. Information about other oral viral infections is sparse. There was a significant benefit of using acyclovir to prevent HSV oral infection (at 800 mg/day). Various dosing protocols of valacyclovir achieved prevention of HSV reactivation (500 or 1,000 mg/day). The prevalence of HSV reactivation was similar for acyclovir and valacyclovir. No information about impact on QOL and economic burden was available. CONCLUSIONS: Acyclovir and valacyclovir are equally effective in preventing oral HSV infection. Neutropenic patients, who were primarily treated for hematological malignancies in the studies reviewed, are at a greater risk for viral infection.

Association of BoLA DRB3 gene polymorphisms with BoHV-1 infection and zootechnical traits.

BACKGROUND: The dairy sector is one of the leading in agricultural production sectors in the world and the bovine herpesvirus 1 (BoHV-1) is an important pathogen that causes great losses in most production systems. Moreover, BoLA DRB3 immunological gene presents different alleles related to protection against many pathogens. METHODS: Serological diagnosis was carried out to determine the BoHV-1 infection and through PCR-RFLP 506 Holstein cows from several municipalities of Antioquia were genotyped for BoLA DRB3.2 gene polymorphisms. RESULTS: Alleles 8, 16, 22, and 24 were the most common out of the 42 alleles found. By indirect ELISA technique, a 58.7% prevalence of BoHV-1 infection in this population was diagnosed and Odd ratios for found alleles were calculated by logistic regression; the only significant association was held for allele 37, which showed that it effects confers susceptibility to infection. On the other hand, by using generalized linear models, a significant association between BoLA DRB3.2 gene and milk and fat yield in primiparous and services per conception in multiparous was found, with the most favorable alleles being 11 and 28 in primiparous and 22 and 28 in multiparous; allele 37 was unfavorable only in primiparous. CONCLUSION: BoLA DRB3.2 gene polymorphisms have shown high variability and significant effects on Holstein cattle and their performance in production systems in Antioquia are at both sanitary or health and productive levels.

Immune protection is dependent on the gut microbiome in a lethal mouse gammaherpesviral infection.

Immunopathogenesis in systemic viral infections can induce a septic state with leaky capillary syndrome, disseminated coagulopathy, and high mortality with limited treatment options. Murine gammaherpesvirus-68 (MHV-68) intraperitoneal infection is a gammaherpesvirus model for producing severe vasculitis, colitis and lethal hemorrhagic pneumonia in interferon gamma receptor-deficient (IFNγR-/-) mice. In prior work, treatment with myxomavirus-derived Serp-1 or a derivative peptide S-7 (G305TTASSDTAITLIPR319) induced immune protection, reduced disease severity and improved survival after MHV-68 infection. Here, we investigate the gut bacterial microbiome in MHV-68 infection. Antibiotic suppression markedly accelerated MHV-68 pathology causing pulmonary consolidation and hemorrhage, increased mortality and specific modification of gut microbiota. Serp-1 and S-7 reduced pulmonary pathology and detectable MHV-68 with increased CD3 and CD8 cells. Treatment efficacy was lost after antibiotic treatments with associated specific changes in the gut bacterial microbiota. In summary, transkingdom host-virus-microbiome interactions in gammaherpesvirus infection influences gammaherpesviral infection severity and reduces immune modulating therapeutic efficacy.

Infection of normal human epithelial cells by Epstein-Barr virus.

Primary cultures of epithelial cells were grown from the tonsils and adenoids of patients with diseases not related to Epstein-Barr virus. The cells could not be infected by Epstein-Barr virus. Fluorescein-labeled Epstein-Barr virus and a cytofluorograph were then used to show that the epithelial cells do not have detectable receptors for the virus. However, implantation with Epstein-Barr virus receptors gave the cells the ability to bind the labeled virus. One to 5 percent of receptor-implanted cells exposed to the transforming B95-8 substrain of the virus expressed Epstein-Barr nuclear antigen. The early and viral capsid Epstein-Barr virus-determined antigens were not detected in the virus-infected cultures. The results show that normal human epithelial cells from the nasopharynx become susceptible to infection by Epstein-Barr virus when the membrane barrier resulting from the lack of viral receptors is overcome by receptor implantation.

Isolation of a new virus, HBLV, in patients with lymphoproliferative disorders.

A novel human B-lymphotropic virus (HBLV) was isolated from the peripheral blood leukocytes of six individuals: two HTLV-III seropositive patients from the United States (one with AIDS-related lymphoma and one with dermatopathic lymphadenopathy), three HTLV-III seronegative patients from the United States (one with angioimmunoblastic lymphadenopathy, one with cutaneous T-cell lymphoma, and one with immunoblastic lymphoma), and one HTLV-III seronegative patient with acute lymphocytic leukemia from Jamaica. All six isolates were closely related by antigenic analysis, and sera from all six virus-positive patients reacted immunologically with each virus isolate. In contrast, only four sera from 220 randomly selected healthy donors and none from 12 AIDS patients without associated lymphoma were seropositive. The virus selectively infected freshly isolated human B cells and converted them into large, refractile mono- or binucleated cells with nuclear and cytoplasmic inclusion bodies. HBLV is morphologically similar to viruses of the herpesvirus family but is readily distinguishable from the known human and nonhuman primate herpesviruses by host range, in vitro biological effects, and antigenic features.

Latent herpes simplex virus in spinal ganglia of mice.

Herpes simplex virus establishes a persistent, latent infection in spinal ganglia after mice have recovered from posterior paralysis. Infectious virus is replicated when these ganglia are explanted and maintained as organ cultures in vitro.

Immunohistochemical and molecular detection of equine herpesvirus 1 in Uruguay.

Equine herpesvirus 1 (EHV-1) is a major cause of epidemic abortion, neonatal mortality, respiratory disease and neurological disorders in horses. In South America, the virus has been isolated in Brazil, Argentina and Colombia. In Chile pathological findings from one aborted foetus have been reported, and in Uruguay only serological data about EHV-1 activity have been found. Some pathological findings were reported in Uruguay several years ago, but these data have never been officially confirmed. The present work describes the relevant findings of a study of EHV-1 infections in the Uruguayan equine population using polymerase chain reaction (PCR) and histological and immunohistochemical analysis techniques. The sequence analysis of a portion of the glycoprotein C gene amplified by PCR confirmed EHV-1 activity. The real-time PCR revealed the association of the virus with the non-neuropathogenic genotype. This study describes for the first time the immunohistochemical and molecular detection of EHV-1 in Uruguay.

Lamella-particle complexes in nuclei of owl monkey kidney cells infected with herpesvirus saimiri.

A complex consisting of ribosome-like particles and a striated lamella occurring in stacked, tubular, and twisted ribbon-like configurations was observed in the nuclei of confluent monolayer cultures of primary owl monkey kidney cells infected with Herpesvirus saimiri. They were similar to the cytoplasmic cylindroid structures seen in some human leukemias and in the lymphoma of the northern pike.

Oncornavirus particles in lymphoid cultures from a howler monkey with Herpesvirus saimiri-induced disease.

Budding and extracellular oncornavirus particles were observed in cells of lymphoid cultures derived from the spleen, lymph node, and blood of a howler monkey (Alouatta caraya) that developed a malignant lymphoproliferative disease after infection with Herpesvirus saimiri. The various possible sources of origin of these particles are discussed.

Mononuclear cell fraction carrying Herpesvirus saimiri in persistently infected squirrel monkeys.

Circulating lymphocytes from squirrel monkeys persistently infected with Herpesvirus saimiri (HVS) were separated into B- and T-lymphocyte fractions by a rosette-enrichment technique. HVS was isolated only from lymphocyte fractions forming rosettes or from unseparated lymphocytes; this indicated that T-lymphocytes were the target cells for HVS in the natural host, squirrel monkeys.

Simultaneous progressive multifocal leukoencephalopathy, Epstein-Barr virus (EBV) latent infection and cerebral parenchymal infiltration during chronic lymphocytic leukemia.

We report a non-HIV patient who had B chronic lymphocytic leukemia (CLL) with progressive multifocal leukoencephalopathy (PML) and diffuse cerebral leukemic parenchymal infiltration in the presence of JC virus and Epstein-Barr virus (EBV) cerebral co-infection. Multiple subcortical hypodensities lining the cortico-subcortical junction were present within the white matter on computerized tomography (CT) scan, with large areas of high signal intensity on T2-weighted sequences on magnetic resonance imaging (MRI). JCV DNA was identified in peripheral blood nuclear cells and cerebrospinal fluid polymerase chain reaction (PCR) DNA/DNA hybridization plus Southern blot analysis. Frontal stereotactic biopsy confirmed the diagnosis of PML by immunocytochemistry, in situ hybridization (ISH) with JC Enzo probe and electron microscopy. Leukemic B cells with the same phenotype as leukemic blood cells were disseminated in the demyelinated areas. They were labeled by anti-latent membrane protein and by BamHl W EBV probe after ISH. Adhesion and activation molecules were positive for CD23. Autopsy showed diffuse visceral leukemic infiltration without acutization. EBV-transformed B lymphocytes would favour JCV penetration and/or intracerebral reactivation of previously latent JCV infection with further development of simultaneous PML and cerebral CLL infiltration in an immunosuppressed patient.

Co-existence of the A and B types of Epstein-Barr virus DNA in lymph node biopsies from Algerian patients with Hodgkin's disease and non-Hodgkin's lymphoma.

The association of Epstein-Barr virus (EBV) with Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) was examined in Algerian patients. The DNA extracted from fresh lymph node biopsies of 17 HD and five NHL was analysed by polymerase chain reaction (PCR). Fifteen out of 17 biopsies (88%) from HD contained EBV genome. Viral type analysis showed the coexistence of A and B types of EBV in 14 biopsies (93%), and the sole presence of A type virus in one biopsy. Among five NHL biopsies examined, four biopsies contained both A and B types of EBV, while one revealed A type-virus only. This co-infection of Algerian HD and NHL patients does not seem to be related with any histologic form of these diseases. The analysis of viral types in the saliva from 12 Algerian healthy individuals revealed six EBV positives with only one A type. Two types of lymphoma in Algeria therefore are closely associated with EBV, and are characterized by coinfection with A and B types of EBV.

Incubation of bovine PMNs with conditioned medium from BHV-1 infected peripheral blood mononuclear cells increases their susceptibility to Mannheimia haemolytica leukotoxin.

Active infection with bovine herpesvirus-1 (BHV-1) increases the susceptibility of cattle to secondary bacterial pneumonia with Mannheimia (Pasteurella) haemolytica A1. In the present study we found that bovine PMNs incubated with conditioned media from BHV-1 infected peripheral blood mononuclear cells (PBMCs) exhibited increased LFA-1 expression, enhanced LKT binding and increased LKT cytotoxicity. These effects were abrogated when the conditioned medium was pre-incubated with an anti-IL-1beta Mab before being added to the PMNs. These findings suggest that BHV-1 infection, and the resulting release of IL-1beta and perhaps other inflammatory cytokines, can stimulate activation of LFA-1 in bystander bovine PMNs, thus enhancing the binding and biological effects of LKT.

Epidemiology of Human Herpes Virus 8 in Pregnant Women and their Newborns--A cross-sectional delivery survey in Central Gabon.

OBJECTIVES: On the background of a high prevalence of HHV-8 infection in pre-pubertal Central African children, this study investigated the potential for in utero transmission of HHV-8. PATIENTS: Gabonese pregnant women were invited to provide peripheral and cord blood samples for serological and PCR diagnostics of HHV-8 infection at delivery for this cross-sectional survey. RESULTS: Out of 344 participants 120 (35%, 95% CI: 30-40%) were serologically positive for HHV-8. 31% (95% CI: 22-40%) of cord blood samples of seropositive women had detectable IgG antibodies. Among all seropositive participants HHV-8 was detected by PCR in one maternal peripheral blood sample at delivery (1%, 95% CI: 0.2-7%) and in none of cord blood samples. There was no association between demographic characteristics and infection status. Similarly, there was no difference in risk for premature delivery, low birth weight, and maternal anaemia in HHV-8 seropositive women. DISCUSSION: These data suggest a high seroprevalence of HHV-8 infection in pregnant women, however viraemia at delivery does not commonly occur in Central Africa. Based on these observations it may be speculated that infection of children may occur more commonly either antepartum or later on in infancy and childhood.