A bovine teat papilloma specimen harboring Deltapapillomavirus (BPV-1) and Xipapillomavirus (BPV-6) representatives

The common occurrence of multiple papillomavirus infections has been shown in several studies involving the human host. However, investigations with the aim of identifying mixed papillomavirus infections in cattle have been conducted only recently. In the current work we describe a co-infection with two different bovine papillomavirus (BPV) types that was identified in a bovine teat papilloma. The skin wart was obtained from a cow belonging to a Brazilian beef herd. A PCR assay was carried out with the FAP primer pair, which amplifies a partial segment of the L1 gene (approximately 478 bp), and the amplicon was submitted to direct sequencing. Because nucleotide sequences with satisfactory quality scores were not obtained, the amplicon was cloned and further sequencing, involving ten selected clones, was performed. The sequence analysis of the cloned inserts revealed the presence of two different BPV types. BPV-1 (Deltapapillomavirus genus) was detected in six clones, while BPV-6 (Xipapillomavirus genus) was detected in four clones. This finding confirms the presence of BPV co-infection associated with cutaneous papillomatosis in cattle

Shared effects of DISC1 disruption and elevated WNT signaling in human cerebral organoids

The development of three-dimensional culture methods has allowed for the study of developing cortical morphology in human cells. This provides a new tool to study the neurodevelopmental consequences of disease-associated mutations. Here, we study the effects of isogenic DISC1 mutation in cerebral organoids. DISC1 has been implicated in psychiatric disease based on genetic studies, including its interruption by a balanced translocation that increases the risk of major mental illness. Isogenic wild-type and DISC1-disrupted human-induced pluripotent stem cells were used to generate cerebral organoids, which were then examined for morphology and gene expression. We show that DISC1-mutant cerebral organoids display disorganized structural morphology and impaired proliferation, which is phenocopied by WNT agonism and rescued by WNT antagonism. Furthermore, there are many shared changes in gene expression with DISC1 disruption and WNT agonism, including in neural progenitor and cell fate markers, regulators of neuronal migration, and interneuron markers. These shared gene expression changes suggest mechanisms for the observed morphologic dysregulation with DISC1 disruption and points to new avenues for future studies. The shared changes in three-dimensional cerebral organoid morphology and gene expression with DISC1 interruption and WNT agonism further strengthens the link between DISC1 mutation, abnormalities in WNT signaling, and neuropsychiatric disease

Multiple bovine papillomavirus infections associated with cutaneous papillomatosis in brazilian cattle herds

Cutaneous papillomatosis is a pathological condition commonly found in cattle and is characterized by the presence of benign proliferative tumors caused by bovine papillomavirus (BPV) infection. While multiple infections with human papillomavirus (HPV) are common in healthy and immunodeficient humans, studies with the aim of identifying mixed infections are still sporadic in veterinary medicine. The aim of this study is to describe the occurrence of multiple BPV infections in cattle affected by cutaneous papillomatosis. Fifteen skin warts were collected from at least two diverse anatomical regions of six bovines with papillomatosis belonging to three cattle herds from the Paraná state in Brazil. The BPV types present in the skin wart samples were determined by a PCR assay performed with the FAP primer pair for partial L1 gene amplification followed by direct sequencing or by cloning and sequencing of the inserts. Sequence analysis of the obtained amplicons allowed the identification of four characterized BPV types (BPV-1, -2, -6, and -8) and three previously described putative new BPV types (BPV/BR-UEL3, BPV/BR-UEL4, and BPV/BR-UEL5). Double infections were identified in four (A, B, D, and E) of the six animals included in this study. In this work, the strategy adopted to evaluate skin warts from diverse anatomical sites of the same animal allowed the identification of multiple infections with two or three different BPV types. The analysis of four animals belonging to a single cattle herd also showed the presence of six different viral types. These results clearly suggest that both multiple papillomaviral infection and a high viral diversity can be as frequent in cattle as in human beings.<br>A papilomatose cutânea é comumente observada nos rebanhos bovinos e caracterizada pela presença de tumores proliferativos benignos causados pela infecção pelo papilomavírus bovino (BPV). Enquanto a infecção múltipla pelo papilomavírus humano (HPV) é um achado comum tanto em seres humanos saudáveis quanto em pacientes com imunodeficiência, na medicina veterinária esses relatos ainda são escassos. O objetivo desse estudo foi descrever a ocorrência de infecções múltiplas pelo BPV em rebanhos afetados pela papilomatose cutânea. Quinze papilomas foram obtidos, de pelo menos duas regiões anatômicas diferentes, de seis bovinos com papilomatose e provenientes de três rebanhos de corte localizados no estado do Paraná, Brasil. Os tipos virais presentes nas lesões foram identificados por PCR, utilizando o par de oligonucleotídeos iniciadores FAP, seguidos de sequenciamento direto ou clonagem e novo sequenciamento dos insertos. A análise das sequências obtidas permitiu a identificação do BPV-1, -2, -6 e -8, além de supostos novos tipos (BPV/BR-UEL3, BPV/BR-UEL4, e BPV/BR-UEL5), descritos anteriormente. Infecções por dois tipos diferentes de BPV foram identificadas em quatro animais (A, B, D e E) dos seis incluídos nesse estudo. A estratégia adotada neste estudo permitiu a identificação de infecção múltipla por dois ou três diferentes tipos virais do BPV no mesmo animal. Além disso, a avaliação de quatro animais de um mesmo rebanho demonstrou a presença de seis tipos virais circulantes. Esses resultados sugerem que tanto as infecções múltiplas quanto a grande diversidade viral podem ser frequentes nos bovinos, assim como o observado nos humanos. O reconhecimento da multiplicidade e complexidade das infecções pelo BPV pode colaborar para o entendimento dos aspectos epidemiológicos, clínicos e imunológicos da papilomatose cutânea nos rebanhos bovinos