Papillomaviruses

Abstract

Papillomaviruses (PVs) are a numerous family of small dsDNA viruses infecting virtually all mammals. PVs cause infections without triggering a strong immune response, and natural infection provides only limited protection against reinfection. Most PVs are part and parcel of the skin microbiota. In some cases, infections by certain PVs take diverse clinical presentations from highly productive self-limited warts to invasive cancers. We propose PVs as an excellent model system to study the evolutionary interactions between the immune system and pathogens causing chronic infections: genotypically, PVs are very diverse, with hundreds of different genotypes infecting skin and mucosa; phenotypically, they display extremely broad gradients and trade-offs between key phenotypic traits, namely productivity, immunogenicity, prevalence, oncogenicity and clinical presentation. Public health interventions have been launched to decrease the burden of PV-associated cancers, including massive vaccination against the most oncogenic human PVs, as well as systematic screening for PV chronic anogenital infections. Anti-PVs vaccines elicit protection against infection, induce cross-protection against closely related viruses and result in herd immunity. However, our knowledge on the ecological and intrapatient dynamics of PV infections remains fragmentary. We still need to understand how the novel anthropogenic selection pressures posed by vaccination and screening will affect viral circulation and epidemiology. We present here an overview of PV evolution and the connection between PV genotypes and the phenotypic, clinical manifestations of the diseases they cause. This differential link between viral evolution and the gradient cancer-warts-asymptomatic infections makes PVs a privileged playground for evolutionary medicine research.

The Biological Impact of Genomic Diversity in Cervical Cancer Development

“…In the infected epithelial cell, PV replication occurs during the S-phase using high-fidelity cellular DNA polymerases with error correction leading to mutation rates close to those of the hosts [1]. However, codon usage varies between species and between genes within the same genome [7], and HPVs do not have the same codon usage preferences of the host, since the viral genome is enriched in A+T [8,9].…”

“…PVs have been isolated from diverse hosts, including mammals, birds, turtles, and snakes, suggesting they infect all amniotes [1]. It is believed that their origin dates to around 350 million years ago and is linked to changes in the epithelium of their ancestral host, the first reptiles.…”

Adaptation of Alpha-Papillomavirus over Millennia

“…The acquisition of this new gene provided to the virus the capacity of immune evasion and downregulated the presentation of viral epitopes, triggering an adaptive radiation that generated the three main branches of the Alpha-PVs. Besides that, it allowed a shift to cutaneous tropism in one of the main branches of the Alpha-PVs [28]. …”

Atividade mucosotrópica do Papilomavírus Humano (HPV) no processo carcinogênico em diferentes sítios de infecção.

“…As manifestações clínicas da infecção pelo HPV dependem de múltiplos fatores, incluindo o tipo viral, o genótipo do hospedeiro, o tipo de epitélio infectado, fatores ambientais como a imunidade do hospedeiro e fatores nutricionais (BRAVO; FÉLEZ-SÁNCHEZ, 2015). As verrugas são as manifestações clínicas mais comuns e características da infecção pelo vírus, podem acometer diversas localizações principalmente a pele, mucosa, região anogenital , mucosas oral e laríngea (LETO et al, 2011).…”

“…Podem apresentar crescimento exofítico semelhante à couve-flor e são, geralmente assintomáticos, os HPVs 6 e 11 são os mais detectados nesse tipo de lesão (BRAVO; FÉLEZ-SÁNCHEZ, 2015;LETO et al, 2011). Mundialmente estima-se 32 milhões de casos novos de verrugas genitais a cada ano, no Brasil estima-se em torno de 1,9 milhão por ano (FEDRIZZI, 2011).…”