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Epstein-Barr virus (EBV) is a ubiquitous gammaherpesvirus etiologically associated with benign and malignant diseases. Since the pathogenic mechanisms of EBV are not fully understood, understanding EBV genetic diversity is an ongoing goal. Therefore, the present work describes the genetic diversity of the lytic gene BZLF1 in a sampling of 70 EBV-positive cases from southeastern Brazil. Additionally, together with the genetic regions previously characterized, the aim of the present study was to determine the impact of viral genetic factors that may influence EBV genetic diversity. Accordingly, the phylogenetic analysis of the BZLF1 indicated two main clades with high support, BZ-A and BZ-B (PP > 0.85). Thus, the BZ-A clade was the most diverse clade associated with the main polymorphisms investigated, including the haplotype Type 1 + V3 (p < 0.001). Furthermore, the multigene phylogenetic analysis (MLA) between BZLF1 and the oncogene LMP1 showed specific clusters, revealing haplotypic segregation that previous single-gene phylogenies from both genes failed to demonstrate. Surprisingly, the LMP1 Raji-related variant clusters were shown to be more diverse, associated with BZ-A/B and the Type 2/1 + V3 haplotypes. Finally, due to the high haplotypic diversity of the Raji-related variants, the number of DNA recombination-inducing motifs (DRIMs) was evaluated within the different clusters defined by the MLA. Similarly, the haplotype BZ-A + Raji was shown to harbor a greater number of DRIMs (p < 0.001). These results call attention to the high haplotype diversity of EBV in southeast Brazil and strengthen the hypothesis of the recombinant potential of South American Raji-related variants via the LMP1 oncogene.

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DNA oncoviruses represent an intriguing subject due to their involvement in oncogenesis. These viruses have evolved mechanisms to manipulate the host immune response, facilitating their persistence and actively contributing to carcinogenic processes. This paper describes the complex interactions between DNA oncoviruses and the innate immune system, with a particular emphasis on the cGAS-STING pathway. Exploring these interactions highlights that DNA oncoviruses strategically target and subvert this pathway, exploiting its vulnerabilities for their own survival and proliferation within the host. Understanding these interactions lays the foundation for identifying potential therapeutic interventions. Herein, we sought to contribute to the ongoing efforts in advancing our understanding of the innate immune system in oncoviral pathogenesis.

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Bovine papillomaviruses are related to cause fibroepithelial proliferations in the skin and mucosae and are associated with economic loss mainly related to poor body condition and reduced milk production. This study aimed to investigate the presence and types of bovine papillomaviruses (BPVs) in cattle sampled in different areas of Costa Rica using molecular techniques. A descriptive study with a non-probability convenience sampling was carried out. A total of 99 papillomatous lesions were collected from 63 animals in 32 farms, and analyzed by polymerase chain reaction, rolling circle amplification (RCA), sequencing, and restriction enzymes digestion. Seven bovine papillomavirus types (BPV1, BPV2, BPV4, BPV6, BPV7, BPV10, BPV11) and two putative novel viral variants (BPV-CR1 and BPV-CR2) were identified for the first time in Costa Rica. BPV6 was the most frequently detected virus in lesions (31.2%), followed by BPV2 (25%) and BPV1 (25%). BPV1 and BPV2 were the most widely distributed in the Country. Coinfections were recorded in two animals (BPV1 / BPV2 and BPV4 / BPV6). Restriction analyses allowed differentiating BPV1 from BPV2, BPV4, and BPV7, but failed to identify BPV6, BPV10, and BPV11. Results suggest that a great PVs diversity is harbored by bovines in Costa Rica and indicate the need for further investigations aimed to uncover PV diversity at the full genomic level.

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BACKGROUND Epstein-Barr virus (EBV) is a human gammaherpesvirus etiologically linked to several benign and malignant diseases. EBV-associated malignancies exhibit an unusual global distribution that might be partly attributed to virus and host genetic backgrounds. OBJECTIVES To assemble a new genome of EBV (CEMO3) from a paediatric Burkitt's lymphoma from Rio de Janeiro State (Southeast Brazil). In addition, to perform global phylogenetic analysis using complete EBV genomes, including CEMO3, and investigate the genetic relationship of some South American (SA) genomes through EBV subgenomic targets. METHODS CEMO3 was sequenced through next generation sequencing and its coverage and gaps were corrected through the Sanger method. CEMO3 and 67 EBV genomes representing diverse geographic regions were evaluated through maximum likelihood phylogenetic analysis. Further, the polymorphism of subgenomic regions of some SA EBV genomes were assessed. FINDINGS The whole bulk tumour sequencing yielded 23,217 reads related to EBV, which 172,713 base pairs of the newly EBV genome CEMO3 was assembled. The CEMO3 and most SA EBV genomes clustered within the SA subclade closely related to the African Raji strain, forming the South American/Raji clade. Notably, these Raji-related genomes exhibit significant genetic diversity, characterised by distinctive synapomorphies at some gene levels absent in the original Raji strain. CONCLUSION The CEMO3 represents a new South American EBV genome assembled. Albeit the majority of EBV genomes from SA are Raji-related, it harbours a high diversity different from the original Raji strain.

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Over the past few decades, several publications have investigated the role of Epstein-Barr virus (EBV) in head and neck squamous cell carcinomas, and an increasing number of them have shown its presence in laryngeal tumors. The purpose of this meta-analysis was to evaluate the association of EBV with laryngeal carcinoma. The search was carried out in two databases, Scopus and PubMed, using the following terms: "Epstein-Barr virus" and "laryngeal carcinoma". A total of 187 records were found, of which 31 were selected for meeting the inclusion and exclusion criteria. The meta-analysis yielded an overall pooled prevalence of 43.72% (95% confidence interval (CI): 34.35-53.08). Studies carried out in Europe and Eurasia had slightly higher pooled prevalence than other subgroups, while the prevalence of studies performed in developed countries was higher than in developing countries (46.37% vs. 34.02%). Furthermore, laryngeal carcinoma occurred almost three times as often among EBV-infected individuals compared to those without EBV infection (odds ratio = 2.86 (95% CI: 1.18-6.90); Begg's test, p = 0.843 and Egger's test, p = 0.866). Our findings support the idea that EBV is related to laryngeal carcinoma. However, further studies are needed before recognizing a definitive etiological role of EBV in the development and/or progression of laryngeal carcinomas.

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Immunotherapy has been shown to be highly effective in some types of cancer caused by viruses. Gene therapy involves insertion or modification of a therapeutic gene, to correct for inappropriate gene products that cause/may cause diseases. Both these types of therapy have been used as alternative ways to avoid cancers caused by oncoviruses. In this review, we summarize recent studies on immunotherapy and gene therapy including the topics of oncolytic immunotherapy, immune checkpoint inhibitors, gene replacement, antisense oligonucleotides, RNA interference, clustered regularly interspaced short palindromic repeats Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-based gene editing, transcription activator-like effector nucleases (TALENs) and custom treatment for Epstein-Barr virus, human T-lymphotropic virus 1, hepatitis B virus, human papillomavirus, hepatitis C virus, herpesvirus associated with Kaposi's sarcoma, Merkel cell polyomavirus, and cytomegalovirus.

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CD8+ T-cell exhaustion is a dysfunctional state that is regulated through the expression of inhibitory checkpoint receptor genes including the cytotoxic T-lymphocyte-associated antigen 4, programmed death 1, and DNA methylation of effector genes interferon-γ, perforin, and granzyme B. Different strategies have been used to reverse T-cell exhaustion, which is an adverse event of checkpoint inhibitor blockade. Here, we present the mechanisms by which DNA methyltransferase inhibitors and Simian virus 40 large T antigen through viral mimicry can promote the reversion of exhausted CD8+ T cells. We examine how these pharmacological strategies can work together to improve the clinical efficacy of immunotherapies.

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The over-expression of immune-suppressors such as IL-10 is a crucial landmark in both tumor progression, and latent viral and parasite infection. IL-10 is a multifunctional protein. Besides its immune-cell suppressive function, it also promotes B-cell tumorigenesis of lymphomas and melanoma. Human pathogens like unicellular parasites and viruses that remain latent inside B cells promote the over-expression of hIL-10 upon infection, which inhibits cell-mediated immune surveillance, and at the same time mediates B cell proliferation. The B-cell specific oncogenic latent virus Epstein-Barr virus (EBV) encodes a viral homologue of hIL-10 (ebvIL-10), expressed during lytic viral proliferation. Once expressed, ebvIL-10 inhibits cell-mediated immune surveillance, assuring EBV re-infection. During long-term latency, EBV-infected B cells over-express hIL-10 to assure B-cell proliferation, occasionally inducing EBV-mediated lymphomas. The amino acid sequences of hIL-10 and ebvIL-10 are more than 80% identical and thus have a very similar tridimensional structure. Based on their published crystallographic structures bound to their human receptor IL10R1, we report a structure-based design of hIL-10 and ebvIL-10 inhibitors based on 3 loops from IL10R1 that establish specific hydrogen bonds with the two IL10s. We have grafted these loops onto a permissible loop in three well-known miniprotein scaffolds-the Conus snail toxin MVIIA, the plant-derived trypsin inhibitor EETI, and the human appetite modulator AgRP. Our computational workflow described in detail below was invigorated by the negative and positive controls implemented, and therefore paves the way for future in vitro and in vivo validation assays of the IL-10 inhibitors engineered.

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An ultrastructural and histological study was performed to determine the degree of differentiation of the neoplastic cells. The histological study revealed neoplastic cells with pleomorphism, oval nuclei, prominent nucleoli, irregularly distributed chromatin, atypical mitotic figures and moderate amount of cytoplasm containing spherical eosinophilic granulations, typical features of the myeloid lineage. Ultrastructurally, there were cells with an electron-dense, oval and voluminous nucleus, with predominant euchromatin and cytoplasm containing many spherical, electron-dense and homogeneous granules, indicative of myelocytes with differentiation to eosinophils. Type-C viral particles were also seen in the intercellular space of renal tubules and inside the intracytoplasmic vesicles of immature myelocytes in the bone marrow and ovary. PCR was positive to ALV-J.(AU)

Caracterizaram-se a linhagem e o grau de diferenciação das células neoplásicas no estudo histopatológico e ultraestrutural da leucose mielóide. Histologicamente as células neoplásicas apresentaram pleomorfismo, núcleos ovais, nucléolos proeminentes, cromatina distribuída de maneira irregular, figuras de mitose atípicas e moderada quantidade de citoplasma contendo granulações eosinofílicas esféricas. Essas características indicam a linhagem mielóide. Ultraestruturalmente evidenciaram-se células com núcleo oval, volumoso, eletrodenso, com predomínio de eucromatina e citoplasma com numerosos grânulos esféricos, eletrodensos e homogêneos, indicando mielócitos com diferenciação para eosinófilos. Constatou-se também a presença de partículas virais tipo-C no espaço intercelular dos túbulos renais, no interior de vesículas intracitoplasmáticas dos mielócitos imaturos presentes na medula óssea e ovário, e PCR positivo para ALV-J.(AU)

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Serum samples of dairy cows from the region of the municipality of Pitangueiras, State of São Paulo, were investigated for the possible presence of precipitating antibodies against the gp51 antigen of Enzootic Bovine Leukosis. Blood samples were obtained from animals belonging to seven rural properties which were followed up on a yearly basis, from 1992 to 1995. A total of 140 serum samples were analyzed in 1992. Of these, 24 (17.1%) reacted positively, 21 (15.0%) were suspect and 95(67.9%) were negative. In 1993, of the 122 samples tested 25 (20.5%) were positive, 8 (6.6%) were suspect and 89 (72.9%) were negative. In 1994, of the 135 samples tested, 45 (33.3%) were positive, 19 (14.1%) were suspect and 71 (52.6%) were negative. Finally, 119 samples of serum were investigated in 1995, 60 of which (50.4%) were positive, 11 (9.2%) were suspect and 48 (40.4%) were negative.These results demonstrate that a sharp increase in the prevalence of Enzootic Bovine Leukosis occurred during the experiment. From the viewpoint of Animal Sanitary Defense, the growing dissemination of the disease in the studied population serves as a warning about the epidemiologic behavior and about the evolution of the diffusion of the disease in Brazil.

Anticorpos précipitantes contra o antígeno gp51 do vírus da Leucose Enzoótica Bovina foram pesquisados em amostras de soros de vacas leiteiras da região do município de Pitangueiras, no Estado de São Paulo. As amostras sanguíneas eram de animais provenientes de sete propriedades rurais que foram acompanhadas anualmente de 1992 até 1995. Durante o ano de 1992 foram analisados 140 soros, dos quais 24 (17,1%) eram reagentes positivos, 21 (15,0%) suspeitos e 95 (67,9%)negativos. Em 1993, dos 122 soros testados, 25 (20,5%) foram positivos, 8 (6,6%) suspeitos e 89 (72,9%) negativos. No ano de 1994 foram testadas 135 amostras, das quais 45 (33,3%) eram positivas, 19 (14,1%) suspeitas e 71 (52,6%) negativas. Finalmente, em 1995, foram analisadas as amostras de 119 animais sendo que 60 (50,4%) eram positivas, 11 (9,2%) suspeitas e 48 (40,4%) negativas. Os resultados obtidos evidenciam que no decorrer do experimento houve um nítidoaumento na prevalência da Leucose Enzoótica Bovina com o passar do tempo. Sob o prisma da Defesa Sanitária Animal, a crescente disseminação da doença na população estudada serve como alerta sobre o comportamento epidemiológico e sobre a evolução na difusão da enfermidade em nosso meio.