Viral perturbations of host networks reflect disease etiology

PLoS Comput Biol. 2012;8(6):e1002531. doi: 10.1371/journal.pcbi.1002531. Epub 2012 Jun 28.

Abstract

Many human diseases, arising from mutations of disease susceptibility genes (genetic diseases), are also associated with viral infections (virally implicated diseases), either in a directly causal manner or by indirect associations. Here we examine whether viral perturbations of host interactome may underlie such virally implicated disease relationships. Using as models two different human viruses, Epstein-Barr virus (EBV) and human papillomavirus (HPV), we find that host targets of viral proteins reside in network proximity to products of disease susceptibility genes. Expression changes in virally implicated disease tissues and comorbidity patterns cluster significantly in the network vicinity of viral targets. The topological proximity found between cellular targets of viral proteins and disease genes was exploited to uncover a novel pathway linking HPV to Fanconi anemia.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Computational Biology
  • Disease / etiology*
  • Disease / genetics
  • Fanconi Anemia / etiology
  • Fanconi Anemia / genetics
  • Fanconi Anemia / virology
  • Genetic Predisposition to Disease
  • Herpesvirus 4, Human / metabolism
  • Herpesvirus 4, Human / pathogenicity
  • Host-Pathogen Interactions / genetics
  • Host-Pathogen Interactions / physiology
  • Human papillomavirus 16 / metabolism
  • Human papillomavirus 16 / pathogenicity
  • Humans
  • Models, Biological*
  • Protein Interaction Maps
  • Viral Proteins / metabolism
  • Virus Diseases / complications*

Substances

  • Viral Proteins