Insights into the mechanism of action of cidofovir and other acyclic nucleoside phosphonates against polyoma- and papillomaviruses and non-viral induced neoplasia

Antiviral Res. 2015 Feb:114:21-46. doi: 10.1016/j.antiviral.2014.10.012. Epub 2014 Oct 30.

Abstract

Acyclic nucleoside phosphonates (ANPs) are well-known for their antiviral properties, three of them being approved for the treatment of human immunodeficiency virus infection (tenofovir), chronic hepatitis B (tenofovir and adefovir) or human cytomegalovirus retinitis (cidofovir). In addition, cidofovir is mostly used off-label for the treatment of infections caused by several DNA viruses other than cytomegalovirus, including papilloma- and polyomaviruses, which do not encode their own DNA polymerases. There is considerable interest in understanding why cidofovir is effective against these small DNA tumor viruses. Considering that papilloma- and polyomaviruses cause diseases associated either with productive infection (characterized by high production of infectious virus) or transformation (where only a limited number of viral proteins are expressed without synthesis of viral particles), it can be envisaged that cidofovir may act as antiviral and/or antiproliferative agent. The aim of this review is to discuss the advances in recent years in understanding the mode of action of ANPs as antiproliferative agents, given the fact that current data suggest that their use can be extended to the treatment of non-viral related malignancies.

Keywords: Acyclic nucleoside phosphonates; Cidofovir; Human papillomavirus; Human polyomaviruses; Non-viral induced neoplasias; PMEG.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Antiviral Agents / pharmacology*
  • Antiviral Agents / therapeutic use
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cidofovir
  • Cytosine / analogs & derivatives*
  • Cytosine / pharmacology
  • Cytosine / therapeutic use
  • Humans
  • Neoplasms / drug therapy*
  • Organophosphonates / pharmacology*
  • Organophosphonates / therapeutic use
  • Papillomaviridae / drug effects*
  • Papillomaviridae / genetics
  • Papillomaviridae / physiology
  • Papillomavirus Infections / drug therapy
  • Papillomavirus Infections / virology
  • Polyomavirus / drug effects*
  • Polyomavirus / genetics
  • Polyomavirus / physiology
  • Polyomavirus Infections / drug therapy
  • Polyomavirus Infections / virology
  • Tumor Suppressor Protein p53

Substances

  • Antineoplastic Agents
  • Antiviral Agents
  • Organophosphonates
  • Tumor Suppressor Protein p53
  • Cytosine
  • Cidofovir