RESUMEN

BACKGROUND Human herpesvirus-8 (HHV-8)-associated diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS), is a rare form of lymphoid malignancy. It poses unique challenges in diagnosis in the setting of human immunodeficiency virus (HIV) infection and concomitant multiorgan dysfunction. CASE REPORT We describe the case of a 26-year-old man who initially presented with pre-syncope and was found to have HIV, with a CD-4 count of 20 cells/µL. His initial clinical presentation was significant for nonspecific symptoms, isolated anemia, and bilateral pleural effusions without gross lymphadenopathy, which was initially attributed to acute HIV infection. However, his hospital course was complicated by anasarca, renal failure, liver dysfunction, pancytopenia, and microscopic hematuria, which required a more comprehensive diagnostic evaluation. Progressive pancytopenia prompted a bone marrow biopsy, which ultimately revealed HHV-8-associated DLBCL, NOS (HDN). We describe his complicated hospital course and eventual diagnosis of HDN. This patient's broad differential diagnoses and overlap among various clinical syndromes posed a significant diagnostic challenge. Additionally, his multiorgan failure limited his treatment options. CONCLUSIONS The management of HHV-8-associated DLBCL, NOS is complex, requiring a multifaceted approach to ensure prompt diagnosis and treatment, especially given difficulty in arriving at an accurate diagnosis due to the significant overlap with other lymphoproliferative disorders and lack of standardized treatment. We highlight the challenges and paucity of data available for management of HDN in the context of a diagnostically challenging case. We discuss the current limitations in diagnosis and treatment of this rare malignancy and the necessity of further investigation, especially in medically complex patients.

Asunto(s)

Infecciones por VIH , Herpesvirus Humano 8 , Linfoma de Células B Grandes Difuso , Humanos , Masculino , Adulto , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/virología , Linfoma de Células B Grandes Difuso/complicaciones , Infecciones por VIH/complicaciones , Infecciones por VIH/diagnóstico , Herpesvirus Humano 8/aislamiento & purificación , Infecciones por Herpesviridae/diagnóstico , Infecciones por Herpesviridae/complicaciones , Diagnóstico Diferencial

RESUMEN

BACKGROUND: Equine herpesvirus (EHV) can cause respiratory, reproductive and neurological diseases in equine animals, including donkeys. The main pathogens responsible for these diseases are EHV type 1 (EHV-1) and EHV-4. In this study, we collected serum samples from 230 donkeys on 27 large-scale donkey farms to detect EHV-1 and EHV-4 antibodies. We analyzed the presence of EHV antibodies based on region, age and season. RESULTS: Out of the 27 farms, 62.96% (17/27) tested positive for EHV. Of the 230 donkeys tested, 2.61% (6/230) were positive only for EHV-1, 5.22% (12/230) were positive only for EHV-4, and 4.78% (11/230) were positive for both EHV-1 and EHV-4. The highest percentage of positive donkeys (21.28%) was found in Dong'e County. The seropositivity rate among donkeys aged 1-4 years was significantly higher compared to the group of donkeys aged 0-1 year (p < 0.05). Additionally, the positive rate was significantly higher in fall and winter compared to spring and summer (p < 0.05). CONCLUSIONS: Altogether, our findings indicate that large-scale donkey farms in the Liaocheng area have a high prevalence of EHV antibodies. Since Liaocheng is an important donkey trading market in Shandong Province, it is crucial to consider the risk of disease transmission based on our test results. This will help in early detection and prevention of EHV outbreaks.

Asunto(s)

Anticuerpos Antivirales , Equidae , Infecciones por Herpesviridae , Herpesvirus Équido 1 , Animales , Equidae/virología , Infecciones por Herpesviridae/veterinaria , Infecciones por Herpesviridae/epidemiología , Infecciones por Herpesviridae/virología , Anticuerpos Antivirales/sangre , China/epidemiología , Estudios Seroepidemiológicos , Herpesvirus Équido 4/aislamiento & purificación , Femenino , Masculino , Prevalencia

RESUMEN

OBJECTIVES: To determine the prevalence and association of HPV and Herpesviruses in saliva and tissue samples of patients with orofacial tumors. METHODS: Biopsies of tumors were done, and saliva samples were collected from patients with orofacial tumors for the determination of viruses using nested multiplex PCR. Independent variables were sex, age, comorbidities, tumor stage, and length of stay. Outcome variables were the presence or absence of herpesviruses and HPV. Descriptive summaries and inferential statistics were done. RESULTS: A hundred patients were included in the study. Prevalence of herpesviruses and HPV were 17.6 % and 57.0 % in tumors, and 48.3 % and 60.0 % in the saliva of patients respectively. Herpesviruses detected included EBV (21.3 %), HHV-7 (11.2 %), CMV (6.7 %), HSV-1 (5.1 %), HSV-2 (1.1 %), VZV (1.1 %), and Kaposi sarcoma virus (0.6 %). The most prevalent HPV genotypes were HPV-42 (29 %), HPV-43 (22.7 %), HPV-52 (22.2 %), HPV-39 (18.8 %), and HPV-18 (9.1 %). The odds of EBV being detected in malignant orofacial tumors were 2 times that of benign orofacial tumors. HPV DNA in the saliva of patients with orofacial tumors was 69.7 %, compared to 18.2 % of the control sample (p < 0.001). The median length of stay for all participants was 6.5 days, those associated with viruses stayed longer. CONCLUSION: There was a high prevalence of Herpesviruses and HPV in saliva and tumor samples of patients with orofacial tumors, signalling some potential for more work to be done in this area.

Asunto(s)

Herpesviridae , Papillomaviridae , Saliva , Humanos , Femenino , Saliva/virología , Masculino , Persona de Mediana Edad , Herpesviridae/aislamiento & purificación , Herpesviridae/genética , Adulto , Papillomaviridae/aislamiento & purificación , Papillomaviridae/genética , Anciano , Biopsia , Adulto Joven , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/epidemiología , Infecciones por Herpesviridae/virología , Infecciones por Herpesviridae/epidemiología , Prevalencia , ADN Viral/análisis , Neoplasias de la Boca/virología , Neoplasias de la Boca/patología , Adolescente , Brasil/epidemiología , Anciano de 80 o más Años , Reacción en Cadena de la Polimerasa Multiplex , Virus del Papiloma Humano

RESUMEN

BACKGROUND: Elephant endotheliotropic herpesvirus (EEHV) infection is the most common cause for lethal hemorrhagic disease in captive juvenile Asian elephants (Elephas maximus). Although EEHV1 is known as the most likely cause of fatal haemorrhagic disease in Asian elephants, EEHV5 was lately involved in lethal cases of haemorrhagic disease in captive elephants. CASE PRESENTATION: Here we report the first death of a four-year old Asian elephant diagnosed with EEHV5 in Germany. Molecular diagnosis yielded detection of EEHV5 DNA in all tested tissues. Histopathological examination revealed typical features of hemorrhagic disease in all examined organs. EEHV5 was sequenced from total DNA isolated from heart tissue by Illumina and Nanopore sequencing. Sequencing data showed 3,881 variants, distributed across the entire genome, compared to the published EEHV5 sequence. CONCLUSIONS: We have detected EEHV5 in a fatal disease case of a male Asian elephant. Whole genome sequencing revealed substantial differences of our DNA isolate compared to available EEHV5 sequences. This report of fatal haemorrhagic disease associated with EEHV5 infection should raise awareness for EEHV5 as an important elephant pathogen. Genome sequencing and downstream SNPs analysis will further encourage future research to understand genetic diversity, pathogenesis and virulence of EEHVs with respect to developing new diagnostic methods, prophylactic strategies, and implementation of surveillance and control measures.

Asunto(s)

Elefantes , Infecciones por Herpesviridae , Herpesviridae , Animales , Elefantes/virología , Infecciones por Herpesviridae/veterinaria , Infecciones por Herpesviridae/virología , Alemania , Masculino , Resultado Fatal , Herpesviridae/genética , Herpesviridae/aislamiento & purificación , Herpesviridae/clasificación , ADN Viral/genética , Genoma Viral/genética , Filogenia , Análisis de Secuencia de ADN , Variación Genética , Secuenciación Completa del Genoma

RESUMEN

Background: Observational studies have suggested that herpes virus infections increase the risk of allograft dysfunction after tissue and organ transplantation, but it is still unclear whether this association is causal. The aim of this study was to assess the causal relationship between four herpes virus infections and allograft dysfunction. Methods: We used two-sample bidirectional Mendelian randomization (MR) to investigate the causality between four herpes virus infections - cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus (HSV) and varicella zoster virus (VZV) - and allograft dysfunction after tissue and organ transplantation. Based on summary data extracted from genome-wide association studies (GWAS), we chose eligible single nucleotide polymorphisms (SNPs) as instrumental variables. The Inverse variance weighted (IVW) method was used as the main analysis method, supplemented by Weighted median and MR-Egger analyses. The MR-PRESSO test, MR-Egger intercept test, heterogeneity test, leave-one-out analysis and funnel plot were used to analyze the sensitivity of MR results. Results: We found EBV early antigen-D (EA-D) antibody levels and shingles were the only two variables associated with an increased risk of allograft dysfunction. No evidence of allograft dysfunction increasing the risk of the four herpes virus infections was observed. Sensitivity analyses confirmed the robustness of our results. Conclusions: Our results suggest that EBV and VZV are involved in graft rejection or dysfunction. However, the relationship between CMV and HSV infections and allograft dysfunction remains unclear and requires further clarification.

Asunto(s)

Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Trasplante de Órganos , Polimorfismo de Nucleótido Simple , Humanos , Trasplante de Órganos/efectos adversos , Infecciones por Herpesviridae/inmunología , Infecciones por Herpesviridae/virología , Aloinjertos , Rechazo de Injerto/inmunología

RESUMEN

Herpesviruses-encoded microRNAs (miRNAs) have been discovered to be essential regulators in viral life cycle, participating in viral replication, latent or lytic infection, and immunological escape. However, the roles of miRNAs encoded by duck plague virus (DPV) are still unknown. Dev-miR-D28-3p is a miRNA uniquely encoded by DPV CHv strain. The aim of this study was to explore the effect of dev-miR-D28-3p on DPV replication and explore the potential mechanisms involved. Our findings demonstrated that transfection of dev-miR-D28-3p mimic into duck embryo fibroblasts (DEFs) effectively suppressed viral copies, viral titers and viral protein expressions during DPV infection, while the results above were reversed after transfection with dev-miR-D28-3p inhibitor. Subsequently, we further discovered that dev-miR-D28-3p specifically bound to DPV-encoded UL27 and inhibited its expression, suggesting that UL27 was the target gene of dev-miR-D28-3p. Finally, we investigated the role of UL27 in DPV replication and found the overexpression of UL27 increased viral copies, viral titers, and viral protein expressions; whereas the opposite results appear when knockdown of UL27. Our findings illustrated a novel mechanism that DPV regulated itself replication via dev-miR-D28-3p, paving the way for exploring the role of DPV-encoded miRNAs.

Asunto(s)

Patos , Fibroblastos , MicroARNs , Replicación Viral , Animales , MicroARNs/genética , MicroARNs/metabolismo , Patos/virología , Fibroblastos/virología , Mardivirus/genética , Mardivirus/fisiología , Proteínas Virales/genética , Proteínas Virales/metabolismo , ARN Viral/genética , Enfermedades de las Aves de Corral/virología , Regulación Viral de la Expresión Génica , Infecciones por Herpesviridae/virología , Infecciones por Herpesviridae/veterinaria

RESUMEN

Human cytomegalovirus (HCMV) is the most common congenital infection. Several HCMV vaccines are in development, but none have yet been approved. An understanding of the kinetics of CMV replication and transmission may inform the rational design of vaccines to prevent this infection. The salivary glands (SG) are an important site of sustained CMV replication following primary infection and during viral reactivation from latency. As such, the strength of the immune response in the SG likely influences viral dissemination within and between hosts. To study the relationship between the immune response and viral replication in the SG, and viral dissemination from the SG to other tissues, mice were infected with low doses of murine CMV (MCMV). Following intra-SG inoculation, we characterized the viral and immunological dynamics in the SG, blood, and spleen, and identified organ-specific immune correlates of protection. Using these data, we constructed compartmental mathematical models of MCMV infection. Model fitting to data and analysis indicate the importance of cellular immune responses in different organs and point to a threshold of infection within the SG necessary for the establishment and spread of infection.

Asunto(s)

Muromegalovirus , Glándulas Salivales , Animales , Glándulas Salivales/virología , Glándulas Salivales/inmunología , Ratones , Muromegalovirus/inmunología , Muromegalovirus/fisiología , Replicación Viral/fisiología , Cinética , Infecciones por Herpesviridae/inmunología , Infecciones por Herpesviridae/virología , Infecciones por Citomegalovirus/inmunología , Infecciones por Citomegalovirus/virología , Infecciones por Citomegalovirus/transmisión , Biología Computacional

RESUMEN

The herpesviruses are the most common infectious agents associated with both primary and secondary cytokine storm syndromes (CSS). While Epstein-Barr Virus (EBV) is most frequently reported in association with CSS, cytomegalovirus (CMV) and many other herpesviruses (e.g., herpes simplex virus, varicella zoster virus, and human herpesviruses 6 and 8) are clearly associated with CSS in children and adults. Immunocompromised hosts, whether due to primary immunodeficiency or secondary immune compromise (e.g., solid organ or stem cell transplantation), appear to be at particularly increased risk of herpesvirus-associated CSS. In this chapter, the association of the non-EBV herpesviruses with CSS will be discussed, including predisposing factors and treatment considerations.

Asunto(s)

Síndrome de Liberación de Citoquinas , Infecciones por Herpesviridae , Herpesviridae , Humanos , Síndrome de Liberación de Citoquinas/inmunología , Síndrome de Liberación de Citoquinas/virología , Infecciones por Herpesviridae/inmunología , Infecciones por Herpesviridae/virología , Infecciones por Herpesviridae/complicaciones , Herpesviridae/inmunología , Herpesviridae/patogenicidad , Herpesviridae/fisiología , Huésped Inmunocomprometido

Asunto(s)

Coinfección , Infecciones por Virus de Epstein-Barr , Infecciones por Herpesviridae , Herpesvirus Humano 4 , Herpesvirus Humano 8 , Linfoma de Células B Grandes Difuso , Humanos , Linfoma de Células B Grandes Difuso/virología , Linfoma de Células B Grandes Difuso/complicaciones , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/virología , Coinfección/virología , Infecciones por Herpesviridae/complicaciones , Infecciones por Herpesviridae/virología , Masculino , Persona de Mediana Edad , Femenino

RESUMEN

Canid alphaherpesvirus-1 (CaHV-1) may cause a highly fatal haemorrhagic disease in neonatal pups and is associated with reproductive, respiratory and ocular disease in older dogs. Although assumed to have a world-wide distribution, there have been few reports of CaHV-1 in Australia. The aim of this study was to investigate the seroprevalence of CaHV-1 in household dogs in a residential suburb in Townsville, as well as in dogs attending two dog shows in the region. Study participants were recruited through door-to-door non-probability sampling (Douglas dogs, n = 185) or invited to participate (Show dogs; n = 76). Dog owners completed a questionnaire that investigated possible risk factors for recent exposure to CaHV-1. A serum sample from each dog was assayed for anti-CaHV-1 antibodies using a commercially available ELISA. Associations between seropositive dogs and owner-reported risk factors were analysed using univariable analysis and multivariable logistic regression models. The seroprevalence of CaHV-1 was 11.4 % (95 % CI 6.8-15.9 %) and 17.1 % (95 % CI 5.5-28.8) for the Douglas and Show dogs, respectively, with a pooled seroprevalence of 13 % (95 % CI 8.3-17.7 %). Dogs that had suffered from conjunctivitis within the previous 3 months or were involved in breeding were more likely to be seropositive to CaHV-1. No other significant risk factors were identified. In conclusion, CaHV-1 is circulating in dogs in North Queensland and may be contributing to foetal and neonatal losses in this region.

Asunto(s)

Enfermedades de los Perros , Infecciones por Herpesviridae , Herpesvirus Cánido 1 , Animales , Perros , Estudios Seroepidemiológicos , Enfermedades de los Perros/epidemiología , Enfermedades de los Perros/virología , Factores de Riesgo , Queensland/epidemiología , Herpesvirus Cánido 1/aislamiento & purificación , Femenino , Masculino , Infecciones por Herpesviridae/veterinaria , Infecciones por Herpesviridae/epidemiología , Infecciones por Herpesviridae/virología , Ensayo de Inmunoadsorción Enzimática/veterinaria , Anticuerpos Antivirales/sangre , Modelos Logísticos

RESUMEN

Primary effusion lymphoma (PEL) is a malignant B-cell lymphoma attributable to Kaposi sarcoma-associated herpesvirus (KSHV) infection. PEL is characterized by invasive behavior, showing recurrent effusions in body cavities. The clinical outcome and typical prognosis in patients with PEL are poor and potentially lethal. Clarification of the pathogenesis in PEL is urgently needed in order to develop novel therapies. PEL cells generally lack B-cell surface markers, and we therefore hypothesized that the B-cell transcription factor, PAX5, would be down-regulated in PEL. The expression of PAX5 is detected from the pro-B to the mature B-cell stage and is indispensable for the differentiation of B-cells. PAX5 was silenced in PEL cells via its promoter methylation. Up-regulation of PAX5 induced several genes coding for B-cell surface marker mRNA, but not protein level. PAX5 inhibited cell growth via G1 cell cycle arrest. PAX5 bound to RB and increased its protein expression. RB/E2F-regulated genes were significantly down-regulated in microarray analysis and PCR experiments. To elucidate the in vivo role of PAX5, we examined the restoration of PAX5 in a PEL mouse model. The ascites volume and organ invasions were significantly suppressed by PAX5 restoration. Reduction of PAX5 has played a crucial role in the oncogenesis of PEL, and PAX5 is a tumor suppressor in PEL. Targeting PAX5 could represent a novel therapeutic strategy for patients with PEL.

Asunto(s)

Puntos de Control del Ciclo Celular , Herpesvirus Humano 8 , Linfoma de Efusión Primaria , Factor de Transcripción PAX5 , Factor de Transcripción PAX5/metabolismo , Factor de Transcripción PAX5/genética , Linfoma de Efusión Primaria/virología , Linfoma de Efusión Primaria/metabolismo , Linfoma de Efusión Primaria/genética , Linfoma de Efusión Primaria/patología , Linfoma de Efusión Primaria/etiología , Animales , Humanos , Herpesvirus Humano 8/genética , Ratones , Puntos de Control del Ciclo Celular/genética , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Genes Supresores de Tumor , Proliferación Celular , Infecciones por Herpesviridae/metabolismo , Infecciones por Herpesviridae/complicaciones , Infecciones por Herpesviridae/genética , Infecciones por Herpesviridae/virología , Regiones Promotoras Genéticas , Modelos Animales de Enfermedad

RESUMEN

CMV drives the accumulation of virus-specific, highly differentiated CD8 memory T cells (memory inflation [MI]). In mice, MI was shown to directly correlate with the CMV infection dose, yet the CMV-associated CD8 MI plateaus over time. It is unclear how MI is regulated with aging. We infected young mice with 102, 104, and 106 PFU of murine CMV and confirmed that MI magnitude was directly proportional to the infectious dose, reaching a setpoint by midlife. By old age, MI subsided, most prominently in mice infected with 106 PFU, and reached statistical parity between groups in 26-mo-old mice. This corresponded to an age-related loss in lymphatic endothelial cells in lymph nodes, recently shown to be sufficient to drive MI in mice. We propose that MI size and persistence over the lifespan is controlled by the size of the lymphatic endothelial cell niche, whose shrinking leads to reduced MI with aging.

Asunto(s)

Linfocitos T CD8-positivos , Memoria Inmunológica , Muromegalovirus , Latencia del Virus , Animales , Ratones , Linfocitos T CD8-positivos/inmunología , Latencia del Virus/inmunología , Memoria Inmunológica/inmunología , Muromegalovirus/inmunología , Envejecimiento/inmunología , Ratones Endogámicos C57BL , Células T de Memoria/inmunología , Infecciones por Citomegalovirus/inmunología , Infecciones por Herpesviridae/inmunología , Células Endoteliales/inmunología , Células Endoteliales/virología , Citomegalovirus/inmunología , Citomegalovirus/fisiología , Ganglios Linfáticos/inmunología

RESUMEN

BACKGROUND: Bovine herpesvirus 1 (BoHV-1) is a major pathogen that affects the global bovine population, primarily inducing respiratory and reproductive disorders. Its ability to establish latent infections in neuronal cells and to reactivate under certain conditions poses a continual threat to uninfected hosts. In this study, we aimed to analyze the replication characteristics of BoHV-1 in neuronal cells, as well as the effects of viral replication on host cell immunity and physiology. METHODS: Using the Neuro-2a neuronal-origin cell line as a model, we explored the dynamics of BoHV-1 replication and analyzed differential gene expression profiles post-BoHV-1 infection using high-throughput RNA sequencing. RESULTS: BoHV-1 demonstrated restricted replication in Neuro-2a cells. BoHV-1 induced apoptotic pathways and enhanced the transcription of interferon-stimulated genes and interferon regulatory factors while suppressing the complement cascade in Neuro-2a cells. CONCLUSIONS: Different from BoHV-1 infection in other non-highly differentiated somatic cells result in viral dominance, BoHV-1 regulated the innate immune response in neuronal cells formed a "virus-nerve cell" relative equilibrium state, which may account for the restricted replication of BoHV-1 in neuronal cells, leading to a latent infection. These findings provide a foundation for further research into the mechanism underlying BoHV-1-induced latent infection in nerve cells.

Asunto(s)

Perfilación de la Expresión Génica , Herpesvirus Bovino 1 , Inmunidad Innata , Neuronas , Replicación Viral , Herpesvirus Bovino 1/inmunología , Herpesvirus Bovino 1/genética , Herpesvirus Bovino 1/fisiología , Animales , Bovinos , Neuronas/virología , Neuronas/inmunología , Línea Celular , Ratones , Infecciones por Herpesviridae/virología , Infecciones por Herpesviridae/inmunología , Infecciones por Herpesviridae/veterinaria , Apoptosis , Transcriptoma , Latencia del Virus , Interacciones Huésped-Patógeno/inmunología , Enfermedades de los Bovinos/virología , Enfermedades de los Bovinos/inmunología , Factores Reguladores del Interferón/genética , Factores Reguladores del Interferón/metabolismo , Secuenciación de Nucleótidos de Alto Rendimiento

RESUMEN

Herpesviruses are DNA viruses and the cause of diseases ranging from mild skin conditions to severe brain diseases. Mammalian antiviral host defense comprises an array of mechanisms, including restriction factors (RFs), which block specific steps in viral replication cycles. In recent years, knowledge of RFs that contribute to controlling herpesvirus infections has expanded significantly, along with a new understanding of viral evasion mechanisms and disease pathogenesis. By integrating findings from human genetics, murine models, and cellular studies, this review provides a current view of RF control of herpesvirus infections. We also explore the regulation of RF expression, discuss the roles of RFs in diseases, and point towards their growing potential as candidate therapeutic targets.

Asunto(s)

Infecciones por Herpesviridae , Humanos , Infecciones por Herpesviridae/inmunología , Infecciones por Herpesviridae/virología , Animales , Herpesviridae/inmunología , Herpesviridae/fisiología , Replicación Viral , Interacciones Huésped-Patógeno/inmunología , Evasión Inmune

RESUMEN

Elephant endotheliotropic herpesvirus (EEHV) causes lethal hemorrhagic disease (HD) in Asian and African elephants. Although rapid detection of viremia and supportive treatments may improve survival rates, an effective vaccine would mitigate the devastating effects of this virus. In elephants, chronic infection with EEHV leads to adaptive immunity against glycoproteins gB and gH/gL, the core entry machinery for most herpesviruses. We previously evaluated two EEHV gB vaccines in mice but not a gH/gL vaccine. Here, we found that inoculation of mice with an adjuvanted EEHV gH/gL subunit vaccine induced a significant antibody response that was similar to the response observed in elephants chronically infected with EEHV. Moreover, the gH/gL heterodimer elicited polyfunctional T cells with a Th1 phenotype but no detectable Th2 response. These results suggest that gH/gL, possibly in combination with gB, may be suitable immunogens for a vaccine comprising herpesvirus glycoproteins that are known to mediate cell entry and infection.

Asunto(s)

Anticuerpos Antivirales , Infecciones por Herpesviridae , Inmunidad Celular , Inmunidad Humoral , Animales , Ratones , Inmunidad Celular/inmunología , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , Infecciones por Herpesviridae/inmunología , Infecciones por Herpesviridae/prevención & control , Inmunidad Humoral/inmunología , Femenino , Proteínas del Envoltorio Viral/inmunología , Vacunas de Subunidad/inmunología , Vacunas contra Herpesvirus/inmunología , Herpesvirus Équido 1/inmunología , Ratones Endogámicos BALB C

RESUMEN

Kaposi's sarcoma-associated herpesvirus (KSHV) establishes persistent infection in the host by encoding a vast network of proteins that aid immune evasion. One of these targeted innate immunity pathways is the cGAS-STING pathway, which inhibits the reactivation of KSHV from latency. Previously, we identified multiple cGAS/STING inhibitors encoded by KSHV, suggesting that the counteractions of this pathway by viral proteins are critical for maintaining a successful KSHV life cycle. However, the detailed mechanisms of how these viral proteins block innate immunity and facilitate KSHV lytic replication remain largely unknown. In this study, we report that ORF48, a previously identified negative regulator of the cGAS/STING pathway, is required for optimal KSHV lytic replication. We used both siRNA and deletion-based systems to evaluate the importance of intact ORF48 in the KSHV lytic cycle. In both systems, loss of ORF48 resulted in defects in lytic gene transcription, lytic protein expression, viral genome replication and infectious virion production. ORF48 genome deletion caused more robust and global repression of the KSHV transcriptome, possibly due to the disruption of RTA promoter activity. Mechanistically, overexpressed ORF48 was found to colocalize and interact with endogenous STING in HEK293 cells. Endogenous ORF48 and STING interactions were also detected in reactivated iSLK.219 cells. Compared with the control cell line, HUVEC cells stably expressing ORF48 exhibited repressed STING-dependent innate immune signaling upon ISD or diABZI treatment. However, the loss of ORF48 in our iSLK-based lytic system failed to induce IFNß production, suggesting a redundant role of ORF48 on STING signaling during the KSHV lytic phase. Thus, ORF48 is required for optimal KSHV lytic replication through additional mechanisms that need to be further explored.

Asunto(s)

Herpesvirus Humano 8 , Proteínas Virales , Replicación Viral , Herpesvirus Humano 8/fisiología , Humanos , Replicación Viral/fisiología , Proteínas Virales/metabolismo , Proteínas Virales/genética , Inmunidad Innata , Células HEK293 , Sarcoma de Kaposi/virología , Sarcoma de Kaposi/metabolismo , Regulación Viral de la Expresión Génica , Latencia del Virus/fisiología , Infecciones por Herpesviridae/metabolismo , Infecciones por Herpesviridae/virología

RESUMEN

Cytomegaloviruses (CMVs) transmit via chronic shedding from the salivary glands. How this relates to the broad cell tropism they exhibit in vitro is unclear. Human CMV (HCMV) infection presents only after salivary gland infection is established. Murine CMV (MCMV) is therefore useful to analyse early infection events. It reaches the salivary glands via infected myeloid cells. Three adjacent spliced genes designated as m131/129 (MCK-2), sgg1 and sgg1.1, positional homologues of the HCMV UL128/130/131 tropism determinants, are implicated. We show that a sgg1 null mutant is defective in infected myeloid cell entry into the salivary glands, a phenotype distinct from MCMV lacking MCK-2. These data point to a complex, multi-step process of salivary gland colonization.

Asunto(s)

Muromegalovirus , Glándulas Salivales , Animales , Glándulas Salivales/virología , Muromegalovirus/genética , Muromegalovirus/fisiología , Ratones , Tropismo Viral , Células Mieloides/virología , Células Mieloides/metabolismo , Proteínas Virales/genética , Proteínas Virales/metabolismo , Infecciones por Herpesviridae/virología , Quimiocinas CC

RESUMEN

Equine herpesvirus-1 (EHV-1) causes respiratory diseases, abortion, and encephalomyelitis in horses. The EHV-1 immediate-early (IE) protein, essential for viral replication, is transactivated by the binding of a multiprotein complex including the open reading frame 12 (ORF12) and some host factors to the IE promoter region. Promoter-associated non-coding RNAs (pancRNAs), which are transcribed from bidirectional promoters, regulate the transcription of neighboring genes in mammals and pathogens. In this study, we identified a novel pancRNA transcribed from across the areas of the 5'-untranslated region and a promoter of EHV-1 IE and named it IE pancRNA. IE pancRNA and mRNA were simultaneously expressed in EHV-1-infected RN33B-A68B2M cells. This pancRNA was also transcribed in RK13 and E. Derm cells, which are highly susceptible to EHV-1 infection. Furthermore, IE pancRNA upregulated IE gene expression in the presence of ORF12, and stable expression of IE pancRNA increased the number of EHV-1-infected RN33B-A68B2M cells. These results suggest that IE pancRNAs facilitate EHV-1 proliferation by promoting IE gene expression.

Asunto(s)

Regulación Viral de la Expresión Génica , Genes Inmediatos-Precoces , Herpesvirus Équido 1 , Regiones Promotoras Genéticas , Replicación Viral , Herpesvirus Équido 1/genética , Animales , Caballos , Línea Celular , ARN sin Sentido/genética , Transcripción Genética , Infecciones por Herpesviridae/veterinaria , Infecciones por Herpesviridae/virología , Enfermedades de los Caballos/virología , Sistemas de Lectura Abierta

RESUMEN

Numerous Aspergillus fumigatus (Af) airborne spores are inhaled daily by humans and animals due to their ubiquitous presence. The interaction between the spores and the respiratory epithelium, as well as its impact on the epithelial barrier function, remains largely unknown. The epithelial barrier protects the respiratory epithelium against viral infections. However, it can be compromised by environmental contaminants such as pollen, thereby increasing susceptibility to respiratory viral infections, including alphaherpesvirus equine herpesvirus type 1 (EHV-1). To determine whether Af spores disrupt the epithelial integrity and enhance susceptibility to viral infections, equine respiratory mucosal ex vivo explants were pretreated with Af spore diffusate, followed by EHV-1 inoculation. Spore proteases were characterized by zymography and identified using mass spectrometry-based proteomics. Proteases of the serine protease, metalloprotease, and aspartic protease groups were identified. Morphological analysis of hematoxylin-eosin (HE)-stained sections of the explants revealed that Af spores induced the desquamation of epithelial cells and a significant increase in intercellular space at high and low concentrations, respectively. The increase in intercellular space in the epithelium caused by Af spore proteases correlated with an increase in EHV-1 infection. Together, our findings demonstrate that Af spore proteases disrupt epithelial integrity, potentially leading to increased viral infection of the respiratory epithelium.

Asunto(s)

Aspergillus fumigatus , Infecciones por Herpesviridae , Herpesvirus Équido 1 , Péptido Hidrolasas , Mucosa Respiratoria , Esporas Fúngicas , Animales , Herpesvirus Équido 1/fisiología , Herpesvirus Équido 1/patogenicidad , Aspergillus fumigatus/enzimología , Caballos , Mucosa Respiratoria/virología , Infecciones por Herpesviridae/virología , Infecciones por Herpesviridae/veterinaria , Péptido Hidrolasas/metabolismo , Enfermedades de los Caballos/virología , Enfermedades de los Caballos/microbiología , Células Epiteliales/virología , Células Epiteliales/microbiología

RESUMEN

A female narrow-ridged finless porpoise (Neophocaena asiaeorientalis) stranded on a beach on Jeju Island showed epithelial proliferative skin lesions on its body. Two false killer whales (Pseudorca crassidens), caught using nets near Gangneung and Samcheok, respectively, had multiple plaques on their penile epidermis. Histological examination of the epidermis revealed that all the lesions had common features, including accentuated rete pegs, ballooning changes, and eosinophilic intranuclear inclusion (INI) bodies. Based on the histopathological results, herpesvirus infection was suspected, and thus further analysis was conducted using herpesvirus-specific primers. Based on nested polymerase chain reaction (PCR) tests using the herpesvirus-detectable primers, the PCR products demonstrated two fragments: a 222-base-pair (bp) sequence of the DNA polymerase gene, SNUABM_CeHV01, showing 96.4% identity with a bottlenose dolphin herpesvirus from the Jeju narrow-ridged finless porpoise; and a 222 bp sequence of the DNA polymerase gene, SNUABM_CeHV02, showing 95.95% identity with the same bottlenose dolphin herpesvirus from the Gangneung and Samcheok false killer whales. The significance of this study lies in its ability to demonstrate the existence of novel cetacean herpesviruses in South Korean seawater, representing an important step forward in studying potentially harmful pathogens that affect endangered whale and dolphin populations.

Asunto(s)

Gammaherpesvirinae , Infecciones por Herpesviridae , Filogenia , Marsopas , Animales , Infecciones por Herpesviridae/veterinaria , Infecciones por Herpesviridae/virología , Marsopas/virología , República de Corea , Gammaherpesvirinae/genética , Gammaherpesvirinae/aislamiento & purificación , Gammaherpesvirinae/clasificación , Femenino , ADN Viral/genética , Análisis de Secuencia de ADN , Reacción en Cadena de la Polimerasa , Datos de Secuencia Molecular