The molecular biology and HPV drug responsiveness of cynomolgus macaque papillomaviruses support their use in the development of a relevant in vivo model for antiviral drug testing

PLoS One. 2019 Jan 25;14(1):e0211235. doi: 10.1371/journal.pone.0211235. eCollection 2019.

Abstract

Due to the extreme tissue and species restriction of the papillomaviruses (PVs), there is a great need for animal models that accurately mimic PV infection in humans for testing therapeutic strategies against human papillomaviruses (HPVs). In this study, we present data that demonstrate that in terms of gene expression during initial viral DNA amplification, Macaca fascicularis PV (MfPV) types 5 and 8 appear to be similar to mucosal oncogenic HPVs, while MfPV1 (isolated from skin) resembles most high-risk cutaneous beta HPVs (HPV5). Similarities were also observed in replication properties during the initial amplification phase of the MfPV genomes. We demonstrate that high-risk mucosal HPV-specific inhibitors target the transient replication of the MfPV8 genomes, which indicates that similar pathways are used by the high-risk HPVs and MfPVs during their genome replication. Taking all into account, we propose that Macaca fascicularis may serve as a highly relevant model for preclinical tests designed to evaluate therapeutic strategies against HPV-associated lesions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use*
  • Cell Line
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • Gene Expression Regulation, Viral
  • Humans
  • Macaca fascicularis / virology*
  • Papillomaviridae / drug effects
  • Papillomaviridae / genetics
  • Papillomaviridae / pathogenicity*
  • Papillomavirus Infections / drug therapy*
  • Papillomavirus Infections / veterinary
  • Papillomavirus Infections / virology
  • Viral Proteins / genetics
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • Viral Proteins

Grants and funding

This study was funded by the Estonian Research Council, http://www.etag.ee/en/, funding numbers PRG198 (recipient Prof. Mart Ustav) and IUT 20-27 (recipient Prof. Andres Merits); and by the Center of Excellence in Molecular Cell Engineering (2014-2020.4.01.15-0013) through the European Regional Development Fund (recipient Prof. Tanel Tenson), http://ec.europa.eu/regional_policy/en/funding/erdf/. The funder provided support in the form of salaries for authors [MU, EMT, AM], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.