Bovine papillomavirus productive infection in cell cultures: First evidences

Abstract

Bovine papillomavirus (BPV) is the etiological agent of bovine papillomatosis (BP), infectious disease, characterized by the presence of multiples papillomas that can regress spontaneously or progress to malignances. Although recognized as mutagen, BPV action following cancer initiation remains few explored, since studies about cancer progression and metastasis are based on cell cultures. The lack of attention to in vitro models is a reflection of the papillomavirus replication paradigm, which is dependent of epithelium cell differentiation. Since 2008, we have explored the potential of cell lines derived from BPV-infected neoplasms as model to study the oncogenic process. In this study, we described BPV productive infection in cell lines derived from cutaneous papilloma, fibropapilloma and esophageal carcinoma (EC) in which BPV DNA sequences were previously detected by PCR. Considering that the immunodetection of L1 capsid protein is the main evidence of productive infection, we analyzed the expression of this protein by immunofluorescence and flow cytometry. Results showed the immunodetection of L1 protein in cell lines derived from cutaneous papilloma, fibropapilloma and EC, but not in cells derived from BPV-free normal skin. We also observed the presence of spherical and electron-dense particles, with 41.02-61.94 nm diameter in cytoplasmic vesicles of cells in the sixth passage of cutaneous papilloma, fibropapilloma and EC, being compatible with the expected BPV morphology. Cells derived from BPV-free normal skin, in turn, showed membranous particles up to 75.00 nm not compatible with BPV morphology. These results suggest the BPV productive infection in cells lines derived from BPV-infected neoplasm, reinforcing that these cells are useful models to study the viral biology and pathogenesis.Correspondence to: Rita de Cassia Stocco, Genetics Laboratory, Butantan Institute, São Paulo, 05503-900, Brazil, Tel: +55 11 2627-9701; e-mail: rita. stocco@butantan.gov.br Highlights• Bovine papillomavirus (BPV) cause multiples papillomas that can regress or progress to malignances;• BPV action following cancer initiation remains few explored;• Identification of BPV L1 capsid protein and virion-like particles in cytoplasmic vesicles of cell lines derived from BPVinfected cutaneous papilloma, fibropapilloma and esophageal carcinoma;• Cell lines derived from BPV-infected neoplasm can be considered useful model to study the viral biology and pathology.

The human papillomavirus (HPV)-related cancer biology: An overview

“…However, 5% of HPV-16-associated respiratory papillomas can progress to cancer [81]. In addition, studies based on bovine papillomavirus (BPV), which is recognized as useful model to study the HPV biology, have been described the productive infection in bovine placenta [136], lymphocytes [137,138] and cell lines derived from primary cultures of papilloma, fibropapilloma and esophageal carcinoma [139]. Altogether, these data suggest the need to review the paradigm of papillomavirus replication biology.…”

Pathomorphology of Papilloma Tumor in Cattle Based on Macroscopic and Microscopic

“…According to Araldi et al [2], the presence of clinical lesions on the skin is a very important indicator for primary diagnosis that needs to be supported by histopathology. Histopathological analysis, papilloma (exophytic), there was moderate to severe hyperkeratosis, squamous epithelial cell proliferation such as finger-like shape in the fibrovascular area, as well as hypergranulosis in the granulosum stratum similar to the report Ayman and Das [17] and Al-Salihi et al [13].…”

“…In young cattle, warts are found around the neck. Papillomatosis is a benign type of neoplasm, for example, skin papilloma, fibro papilloma and also malignancy, for example, bladder cancer in cattle which causes considerable economic losses [1,2]. Bovine papillomatosis is a disease that attacks cattle with Papilloma (Warts) on the skin and mucosa caused by Bovine Papilloma Virus (BPV) subtypes 1, 2, 3, 4, 5, 6 which were isolated [3].…”

Clinico‐histopathological and molecular detection of small ruminants’ papillomaviruses in Iran

“…It seems to involve exposure to sunlight (Smith, 2022). PVs cause benign and malignant tumours in ruminants, such as cutaneous papilloma, oesophageal, urinary bladder disease, or benign fibroplasia, leading to significant economic losses (Araldi, Melo et al, 2017; Bocaneti et al., 2016). Due to the decrease in milk and meat production and the low value of hides, the incidence of papillomavirus infection may result in significant economic losses for animals.…”