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Enzootic nasal tumor (ENT) is a contagious neoplasm associated with enzootic nasal tumor virus (ENTV), which may induce disease in sheep (ENTV-1) and goats (ENTV-2). This study aimed to describe the occurrence of ENT in two Texel sheep (Ovis aries) from a 75-sheep flock, located in the city of Gravataí, southern Brazil. Animals used to be purchased from different origins, and no specific tests for disease monitoring or quarantine procedure were performed. Affected animals presented respiratory distress, anorexia with severe weight loss, and mucopurulent unilateral nasal discharge. Necropsy was performed in both animals and nasal cavity masses were observed. Histopathological analysis demonstrated an epithelial neoplasm compatible with nasal adenocarcinoma. PCR using a protocol that amplifies a 591 bp sequence of 5'LTR-gag region of ENTV1 was performed followed by DNA sequencing. Both samples were positive, and the sequences obtained presented highest identity (97%) with ENTV strain TN28 (GenBank accession number MH899613) detected in a Texel sheep from Scotland. This is the first report of ENTV-1 leading to enzootic nasal tumor in sheep in Latin America, which confirms the presence of the retrovirus in sheep flocks in the Brazilian territory.

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Human papillomavirus (HPV), an etiological agent of cervical cancer (CC), has infected humans since ancient times. Amerindians are the furthest migrants out of Africa, and they reached the Americas more than 14,000 years ago. Some groups still remain isolated, and some migrate to towns, forming a gradient spanning urbanization. We hypothesized that, by virtue of their history, lifestyle, and isolation from the global society, remote Amerindian women have lower HPV diversity than do urban women (Amerindian or mestizo). Here we determined the diversity of the 25 most relevant cervical HPV types in 82 Amerindians spanning urbanization (low, medium, and high, consistent with the exposure to urban lifestyles of the town of Puerto Ayacucho in the Venezuelan Amazonas State), and in 29 urban mestizos from the town. Cervical, anal, oral, and introitus samples were taken, and HPVs were typed using reverse DNA hybridization. A total of 23 HPV types were detected, including 11 oncogenic or high-risk types, most associated with CC. Cervical HPV prevalence was 75%, with no differences by group, but Amerindians from low and medium urbanization level had significantly lower HPV diversity than mestizos did. In Amerindians, but not in mestizos, infections by only high-risk HPVs were higher than coinfections or by exclusively low-risk HPVs. Cervical abnormalities only were observed in Amerindians (9/82), consistent with their high HPV infection. The lower cervical HPV diversity in more isolated Amerindians is consistent with their lower exposure to the global pool, and transculturation to urban lifestyles could have implications on HPV ecology, infection, and virulence.IMPORTANCE The role of HPV type distribution on the disparity of cervical cancer (CC) incidence between human populations remains unknown. The incidence of CC in the Amazonas State of Venezuela is higher than the national average. In this study, we determined the diversity of known HPV types (the viral agent of CC) in Amerindian and mestizo women living in the Venezuelan Amazonas State. Understanding the ecological diversity of HPV in populations undergoing lifestyle transformations has important implication on public health measures for CC prevention.

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El cáncer se ha convertido en la primera causa de morbimortalidad en numerosos países. En las últimas décadas se ha asistido a un cambio en el paradigma conceptual de las enfermedades neoplásicas, que ahora se enfoca hacia la perspectiva ecológica-evolutiva de estas. Con el objetivo de analizar, con elementos actualizados, la relación entre el proceso evolutivo del ser humano y su predisposición al cáncer, se realizó una revisión sistemática de la literatura, a partir de tres bases de datos, Medline, Scopus, y SciELO. Se tuvieron en cuenta atributos de consistencia de los artículos revisados, se excluyeron los estudios con niveles IV y V de evidencia y los de calidad insuficiente. Las búsquedas acumuladas actuales sugieren la necesidad de ver a las diversas neoplasias desde la perspectiva de la dinámica de sistemas complejos y sus implicaciones evolutivas. El proceso evolutivo humano posee particularidades biosociales que le predisponen a sufrir tumores malignos. La postura bípeda incrementó vulnerabilidad al efecto oncogénico de las radiaciones ultravioletas. La conducta sexual incrementó el riesgo de contraer infecciones por virus oncogénicos. El paso a una predominantemente cárnica y la introducción de la cocción, se tradujo en la incorporación de agentes xenobióticos cuyo metabolismo deriva agentes carcinógenos. La postergación del envejecimiento humano devino en un mayor tiempo para el acúmulo de mutaciones. Las modificaciones en el patrón sexual y reproductivo en la mujer han influido en su predisposición al cáncer de mama. En la génesis poblacional del cáncer subyacen fundamentos biosociales vinculados al proceso evolutivo de la especie(AU)

Cancer has become the leading cause of morbidity and mortality in many countries. In recent decades there has been a change in the conceptual paradigm of neoplastic diseases, which now focuses on the ecological-evolutionary perspective of these. With the aim of analyzing, with updated elements, the relationship between the evolutionary process of the human being and his predisposition to cancer, a systematic review of the literature was made, based on three databases, Medline, Scopus, and SciELO. Consistency attributes of the reviewed articles were taken into account, studies with levels IV and V of evidence and those of insufficient quality were excluded. The current accumulated searches suggest the need to see the various neoplasms from the perspective of the dynamics of complex systems and their evolutionary implications. The human evolutionary process has biosocial peculiarities that predispose it to suffer malignant tumors. Bipedal posture increased vulnerability to the oncogenic effect of ultraviolet radiation. Sexual behavior increased the risk of contracting oncogenic virus infections. The transition to a predominantly meat and the introduction of cooking, resulted in the incorporation of xenobiotic agents whose metabolism derives carcinogens. The postponement of human aging became in a longer time for the accumulation of mutations. Modifications in the sexual and reproductive pattern in women have influenced their predisposition to breast cancer. In the population genesis of cancer underlying biosocial foundations linked to the evolutionary process of the species(AU)

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Two groundbreaking reports were published in Acta Cytologica at the transition of 1976 to 1977. One appeared in the last issue of 1976 [Meisels and Fortin: Acta Cytol 1976;20:505-509] and the other in the first issue of 1977 [Purola and Savia: Acta Cytol 1977;21:26-31]. Today, 40 years later, it is not an overstatement to conclude that these are the two most influential studies ever published in this journal. Two reports with a similar content being published so close together (in the same journal) raised the question "Which of the two reports was truly submitted first?" In this commentary, this enigma is clarified beyond reasonable doubt, based on the well-considered testimonial of Prof. Leopold G. Koss, the reviewer of one of the two papers. To fully appreciate the significance of the novel discovery made in these two reports, it is essential to align them in the right context, both retrospectively and prospectively. This commentary will assist the reader by summarizing the existing knowledge on human papillomavirus (HPV) before these two milestone papers appeared, and describe the incredibly rapid progress that they evoked during the subsequent decades, which made HPV the single most important human tumor virus. As the final proof of virus-cancer causality, prophylactic HPV vaccines have been effective in preventing (a) virus transmission and HPV infection, (b) benign HPV-induced tumors (genital warts), and (c) cervical intraepithelial neoplasia (CIN). Formal evidence of the prevention of cervical cancer by these HPV vaccines still awaits confirmation, and the same applies to the eventual prevention of human cancers at other anatomic sites, part of the global burden of oncogenic HPVs.

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Nucleic acid recognition by toll-like receptor 9 (TLR9) initiates signaling pathways that regulate the production of proinflammatory cytokines or type I interferons, as well as many other molecules required to initialize the immune response. The use of synthetic oligodeoxynucleotides (ODNs) has been crucial to emulate the recognition of DNA sequences by TLR9. Furthermore, ODN administration to mice has shown to confer protection against a wide range of viral, bacterial, and parasitic pathogens. In contrast, oncogenic DNA viruses like hepatitis B virus, Epstein-Barr virus, and human papilloma virus inhibit TLR9 expression, thus contributing to the establishment of chronic viral infections. In this review, we will focus on TLR9 signals initiated by ODN recognition, on the inhibition of TLR9 expression mediated by DNA oncogenic viruses, and on TLR9 expression as a relevant event in the progression to cancer, considering other functions of this receptor, aside from viral recognition.

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Marek's disease (MD) is a lymphoproliferative disorder caused by Gallid herpesvirus 2 (MDV) that infects mainly domestic gallinaceous birds although wild birds may occasionally be affected. The current report describes the anatomopathological and molecular findings of a case of MD in a white-peafowl (Pavo cristatus). The signs included apathy, hyporexia, and diarrhea. Grossly, 0.5 to 1.5cm in diameter, yellow, soft nodules were observed in the skeletal muscle, lung, kidney, air sacs, small intestine, heart, ovary, ventriculus, and proventriculus. Microscopically, numerous atypical round neoplastic cells were noted. The molecular detection of MDV DNA was implemented to amplify part of the meq gene and products were sequenced for the phylogenetic analysis. Template DNA was obtained from tissues of the affected bird and from blood of all the gallinaceous birds of the Zoo. The expected amplicon for the partial amplification of MDV meq gene was obtained and the amplicons were sequenced. Sequences obtained enabled grouping the strain (accession no. KT768121) with MDV serotype 1 strains from the GenBank. Based on the anatomopathological and molecular findings, the diagnosis of MD in a white-peafowl was reached, and to the authors' knowledge, no previous report regarding MD was published in Pavo cristatus.(AU)

Doença de Marek (MD) é uma desordem linfoproliferativa causada pelo Gallid herpesvirus 2 (MDV), que infecta principalmente galináceos domésticos, porém aves silvestres podem ser ocasionalmente afetadas. O presente relato descreve os achados anatomopatológicos e moleculares de um caso de MD em um pavão-branco (Pavo cristatus). Os sinais clínicos incluíram apatia, hiporexia e diarreia. Macroscopicamente, foram observados nódulos macios, de 0,5 a 1,5cm de diâmetro, no músculo esquelético, no pulmão, nos rins, nos sacos aéreos, no intestino delgado, no coração, no ovário, no ventrículo e no proventrículo. Microscopicamente, numerosas células redondas neoplásicas atípicas foram notadas. A detecção molecular do DNA do MDV foi implementada para amplificar parte do gene meq, e os produtos foram sequenciados para análise filogenética. DNA foi obtido de tecidos de aves afetadas e do sangue de todos os galináceos do zoológico. A esperada amplificação de parte do gene meq de MDV amplificado foi ampliada e sequenciada. As sequências obtidas permitiram o agrupamento da cepa (acesso KT768121) com cepas do sorotipo 1 de MDV do GenBank.. O diagnóstico de MD em pavão-branco foi obtido com base nos achados anatomopatológicos e moleculares e, pelo conhecimento dos autores, não há relatos anteriores publicados de MD em Pavo cristatus.(AU)

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Marek's disease (MD) is a lymphoproliferative disorder caused by Gallid herpesvirus 2 (MDV) that infects mainly domestic gallinaceous birds although wild birds may occasionally be affected. The current report describes the anatomopathological and molecular findings of a case of MD in a white-peafowl (Pavo cristatus). The signs included apathy, hyporexia, and diarrhea. Grossly, 0.5 to 1.5cm in diameter, yellow, soft nodules were observed in the skeletal muscle, lung, kidney, air sacs, small intestine, heart, ovary, ventriculus, and proventriculus. Microscopically, numerous atypical round neoplastic cells were noted. The molecular detection of MDV DNA was implemented to amplify part of the meq gene and products were sequenced for the phylogenetic analysis. Template DNA was obtained from tissues of the affected bird and from blood of all the gallinaceous birds of the Zoo. The expected amplicon for the partial amplification of MDV meq gene was obtained and the amplicons were sequenced. Sequences obtained enabled grouping the strain (accession no. KT768121) with MDV serotype 1 strains from the GenBank. Based on the anatomopathological and molecular findings, the diagnosis of MD in a white-peafowl was reached, and to the authors' knowledge, no previous report regarding MD was published in Pavo cristatus.(AU)

Doença de Marek (MD) é uma desordem linfoproliferativa causada pelo Gallid herpesvirus 2 (MDV), que infecta principalmente galináceos domésticos, porém aves silvestres podem ser ocasionalmente afetadas. O presente relato descreve os achados anatomopatológicos e moleculares de um caso de MD em um pavão-branco (Pavo cristatus). Os sinais clínicos incluíram apatia, hiporexia e diarreia. Macroscopicamente, foram observados nódulos macios, de 0,5 a 1,5cm de diâmetro, no músculo esquelético, no pulmão, nos rins, nos sacos aéreos, no intestino delgado, no coração, no ovário, no ventrículo e no proventrículo. Microscopicamente, numerosas células redondas neoplásicas atípicas foram notadas. A detecção molecular do DNA do MDV foi implementada para amplificar parte do gene meq, e os produtos foram sequenciados para análise filogenética. DNA foi obtido de tecidos de aves afetadas e do sangue de todos os galináceos do zoológico. A esperada amplificação de parte do gene meq de MDV amplificado foi ampliada e sequenciada. As sequências obtidas permitiram o agrupamento da cepa (acesso KT768121) com cepas do sorotipo 1 de MDV do GenBank.. O diagnóstico de MD em pavão-branco foi obtido com base nos achados anatomopatológicos e moleculares e, pelo conhecimento dos autores, não há relatos anteriores publicados de MD em Pavo cristatus.(AU)

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INTRODUCTION: Natural Killer cells (NK) are key for the innate immune response against tumors and viral infections. Several viral proteins evade host immune response and target the NK cell receptor NKG2D and its ligands. Areas covered: This review aimed to describe the viruses and their proteins that interfere with the NKG2D receptor and their ligands, and how these interactions lead to immune evasion, host protection, and tissue damage from acute and chronic viral infections. Expert opinion: The study of viral proteins has already impacted the field of oncology. A prime example is the HBV vaccine and the development of antiviral drugs for HIV, Hepatitis C, and the family of Herpesviridae viruses. The NKG2D system seems to be a rational therapeutic target. Nevertheless, an effective cytotoxic response by NK cells is mediated by a network of activating and inhibitory receptors, the integration of which determines if the NK cell becomes cytotoxic or permissive. Immunotherapeutic agents that increase the antitumor lytic activity of NK cells through modulating activation and inhibitory signaling of NK cells are being developed. Nevertheless, more research is needed to dissect the integrative mechanism of NK cells function to fully exploit their antitumor and antiviral effector mechanisms.

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