Papillomaviruses: a systematic review

Abstract

In the last decades, a group of viruses has received great attention due to its relationship with cancer development and its wide distribution throughout the vertebrates: the papillomaviruses. In this article, we aim to review some of the most relevant reports concerning the use of bovines as an experimental model for studies related to papillomaviruses. Moreover, the obtained data contributes to the development of strategies against the clinical consequences of bovine papillomaviruses (BPV) that have led to drastic hazards to the herds. To overcome the problem, the vaccines that we have been developing involve recombinant DNA technology, aiming at prophylactic and therapeutic procedures. It is important to point out that these strategies can be used as models for innovative procedures against HPV, as this virus is the main causal agent of cervical cancer, the second most fatal cancer in women.

Figure 1. BPV genome organization and differential protein expression: double strand DNA circular genome divided in early (E), late (L) and long codon region (LCR). Early region codifies replication proteins (E1, E2, E4, E5, E6 and E7). These proteins are expressed from basal to cornified layer, being involved with virus replication and virion release (E4). Late region codifies L1 and L2 capsid proteins. Once these structural proteins are involved with virus assembly, they are expressed in the most differenciated epithelium layers (granular and cornified).

Figure 2. Adult bovine (Simmental breed) with bovine papillomatosis (BP): skin papillomas on face (A), dewlap (B) and back (C).

Figure 3. Evidences of BPV presence in peripheral blood and cell culture showing: A) amplicon of BPV identified using specific primers for BPV-1, 2 and 4 (Araldi et al., 2013); B) BPV genome identification by chromogenic in situ hybridization (Melo et al., 2015); C) BPV virions identified in cytoplasmic vesicles of PBMCs (Melo et al., 2015); D) Immunodetection of BPV L1 and E2 in lymphocytes (Melo et al., 2015); E) cytogenetic aberrations (breaks) observed in BPV-infected lymphocyte (Stocco dos Santos et al., 1998), F) class 2 nucleoids observed in BPV-infected lymphocytes (Araldi et al., 2013); G) BPV DNA sequences identified in cell culture, using FAP59/64 degenerate primers; H) Immunodetection of BPV early proteins (E1^E4, E2, E7) in both oesophageal and urinary bladder carcinoma cell line (Melo et al., data not published); I) BPV virion, with 55 nm, in cytoplasmic vesicle of cutaneous papilloma cell line, total magnification of 60000X (Melo et al., data not published); J) bovine epithelial cell line (CRIB) treated with E6 recombinant oncoprotein showing micronucleus presence (Araldi et al., 2015a); K) cytogenetic aberration observed in BPV-infected cell line (Campos et al., 2013); L) class 2 nucleoids observed in cutaneous papilloma cell line (Araldi et al., data not published).