**3. Genomic organization**

In the 1970s, the cloning of PVs genomes contributed substantially to the study of their biological and biochemical properties. Sequencing of the cloned genomes allowed the identification of different ORFs as probable viral genes [7].

the DNA strands serves as a template for transcription. The coding strand might exhibit up to 10 ORFs, which are classified according to the cell differentiation stage when they are ex‐ pressed by means of the letters E (early) and L (late). The early genomic segment (E) comprises up to eight ORFs, which are expressed in epithelial cells in the early stages of maturation.The


*Phipapillomavirus Capra hircus Papillomavirus 1 Capra hircus Papillomavirus 1*

*Canis familiaris Papillomavirus 3*

*Dyodeltapapillomavirus Sus scrofa Papillomavirus 1 Sus scrofa Papillomavirus 1 Dyothetapapillomavirus Felis domesticus Papillomavirus 2 Felis domesticus Papillomavirus 2 Dyoiotapapillomavirus Equus caballus Papillomavirus 2 Equus caballus Papillomavirus 2*

**Genera Species Viral Strains**

*Bos taurus Papillomavirus 1 Bos taurus Papillomavirus 2*

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*Ovis aries Papillomavirus 1 Ovis aries Papillomavirus 2*

*Bos taurus Papillomavirus 5 Bos taurus Papillomavirus 8*

*Bos taurus Papillomavirus 3 Bos taurus Papillomavirus 4 Bos taurus Papillomavirus 6 Bos taurus Papillomavirus 9 Bos taurus Papillomavirus 10 Bos taurus Papillomavirus 11 Bos taurus Papillomavirus 12*

*Canis familiaris Papillomavirus 2 Canis familiaris Papillomavirus 7*

*Canis familiaris Papillomavirus 3 Canis familiaris Papillomavirus 5*

*Bos taurus Papillomavirus 1*

*Ovis aries Papillomavirus 1*

*Zetapapillomavirus Equus caballus Papillomavirus 1 Equus caballus Papillomavirus 1*

*Canis familiaris Papillomavirus 1 Canis familiaris Papillomavirus 1 Canis familiaris Papillomavirus 6 Canis familiaris Papillomavirus 6 Felis domesticus Papillomavirus 1 Felis domesticus Papillomavirus 1*

*Canis familiaris Papillomavirus 4 Canis familiaris Papillomavirus 4*

*Epsilonpapillomavirus Bos taurus Papillomavirus 5*

*Xipapillomavirus Bos taurus Papillomavirus 3*

*Taupapillomavirus Canis familiaris Papillomavirus 2*

**Table 3.** Papillomavirus species that infect domestic animals. Source: Adapted from [3].

*Deltapapillomavirus*

*Lambdapapilloamvirus*

*Chipapillomavirus*

The genomic organization of the various PVs is notably similar. A common feature of PVs is that all of the ORFs are contained on a single strand of the viral DNA. Therefore, only one of


**Table 3.** Papillomavirus species that infect domestic animals. Source: Adapted from [3].

**Genera Species**

116 Current Issues in Molecular Virology - Viral Genetics and Biotechnological Applications

**Table 2.** Classification of *Papillomaviridae* family. Source: [3].

animals.

and medical properties [5,6].

**3. Genomic organization**

identification of different ORFs as probable viral genes [7].

*Sigmapapillomavirus Erethizon dorsatum Papillomavirus 1 Taupapillomavirus Canis familiaris Papillomavirus 2 Upsilonpapillomavirus Tursiops truncatus Papillomavirus 1* and *2 Phipapillomavirus Capra hircus Papillomavirus 1 Chipapillomavirus Canis familiaris Papillomavirus 3* and *4 Psipapillomavirus Rousettus aegyptiacus Papillomavirus 1 Omegapapillomavirus Ursus maritimus Papillomavirus 1 Dyodeltapapillomavirus Sus scrofa Papillomavirus 1 Dyoepsilonpapillomavirus Francolinus leucoscepus Papillomavirus 1 Dyozetapapillomavirus Caretta caretta Papillomavirus 1 Dyoetapapillomavirus Erinaceus europaeus Papillomavirus 1 Dyothetapapillomavirus Felis domesticus Papillomavirus 2 Dyoiotapapillomavirus Equus caballus Papillomavirus 2*

PVs isolated from vertebrates are classified into 24 genera, whereas viral species that occur exclusively in birds and reptiles are grouped into three genera and one genus, respectively. The taxonomic nomenclature of animal PV types is based on the scientific name of their hosts according to the genus and species. For example, FdPV1 is the name given to PV of the domestic cat (*Felis domesticus*) type 1 [3]. An exception occurs in the case of the bovine papillomavirus, which was named *Bos taurus* papillomavirus but by consensus is usually referred to as BPV. Table 3 describes the genera and species of PVs identified in various species of domestic

Because PVs are not amenable to isolation using classic cell culture techniques and do not induce a strong humoral immune response in their hosts, the taxonomic terms "strain" and "serotype" were not originally applied to this virus family. Consequently, the family classifi‐ cation is based on the similarities between nt sequences and a limited number of biological

In the 1970s, the cloning of PVs genomes contributed substantially to the study of their biological and biochemical properties. Sequencing of the cloned genomes allowed the

The genomic organization of the various PVs is notably similar. A common feature of PVs is that all of the ORFs are contained on a single strand of the viral DNA. Therefore, only one of the DNA strands serves as a template for transcription. The coding strand might exhibit up to 10 ORFs, which are classified according to the cell differentiation stage when they are ex‐ pressed by means of the letters E (early) and L (late). The early genomic segment (E) comprises up to eight ORFs, which are expressed in epithelial cells in the early stages of maturation.The late segment (L) usually contains two ORFs that are expressed in differentiated keratinocytes. A third region without ORFs has been identified in all PV genomes and is named the LCR (long control region) or URR (upstream regulatory region).This region contains the origin of replication and elements that control transcription (Figure 2) [1].

Transformation studies using BPV1 have shown that the presence of an intact E1 ORF is crucial for the maintenance of viral genome stability in cells through the presence of multiple genomic

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However, the interaction between protein E1 and the origin of replication exhibits low specificity. Specific and efficient recognition of the origin of replication occurs exclusively through the cooperative binding of proteins E1 and E2 to sites adjacent to the origin of replication. Therefore, protein E2 participates in this mechanism as an aggregation factor that

The BPV1 E2 ORF encodes a protein that comprise the central viral regulatory system and thus control genetic expression and viral replication. Protein E2 also modulates the transcription of the early viral promoters through its binding sites [14]. In addition, E2 participates in the maintenance of the viral genome in its episomal form by promoting binding between these

The non-structural protein E4 occurs abundantly in the cytoplasm of the differentiated keratinocytes of papillomas. Therefore, although the gene that encodes this protein is located in the early viral genome region, E4 is produced later in the differentiation process. The E4 protein of HPV16 has also been associated with the collapse of cytokeratin filaments, which

In humans, the oncoproteins E5, E6, and E7 encoded by the genomes of certain HPVs, represent the primary viral factors related to the onset and progression of cervical cancer. These genetic products are able to override the negative regulation of cell growth that is mediated by host cell proteins. In addition, it is believed that these viral oncoproteins promote the genomic

Binding with proteins of the retinoblastoma family is the main mechanism by which protein E7 contributes to the escape of infected cells from the negative regulatory mechanisms of cell growth. In the case of HPV, protein E7 interacts with these cellular factors and targets them for degradation [18]. The result of such binding and degradation is the release and activation of E2F transcription factors that regulate the expression of genes during S phase of the cell cycle. Efficient interaction between E7 and these factors triggers a compensatory inhibition of cell growth and apoptosis that is mediated by the p53 tumor suppressor protein-dependent

The targeting of protein p53 for degradation by viral protein E6 in high-risk HPVs eliminates the inhibition of cell growth in both undifferentiated and differentiated cells [17]. The actions of the viral proteins E6 and E7 to abrogate these regulatory factors of the cell cycle allow infected cells undergoing differentiation to remain in S phase. As a result, many cell cycle checkpoints are abrogated. Consequently, an accumulation of mutations and progression into

cancer occurs in cells that are persistently infected by these viruses [19].

promotes the recruitment of helicase E1 to the origin of replication [13].

thus suggests an auxiliary function in the process of viral exit from cells [1].

genomes and mitotic chromosomes during cell division [15,16].

copies in episomal form [10,11,12].

**4.2. Protein E4**

pathway [17].

**4.3. Proteins E5, E6 and E7**

instability observed in HPV-related cancers [17].

**Figure 2.** Schematic representation of genome of bovine papillomavirus type 1 (BPV1).

Expression of the six most common non-structural and regulatory proteins (E1, E2, E4, E5, E6, and E7), which are encoded by the early viral genome region, occurs in basal cells or during the intermediate stages of maturation. The expression of the two viral structural proteins (L1 and L2) encoded by the late genomic segment occurs in keratinocytes in the final stage of maturation [8].
