Genetic Profiling and Comorbidities of Zika Infection

J Infect Dis. 2017 Sep 15;216(6):703-712. doi: 10.1093/infdis/jix327.


Background: The difficulty in distinguishing infection by Zika virus (ZIKV) from other flaviviruses is a global health concern, particularly given the high risk of neurologic complications (including Guillain-Barré syndrome [GBS]) with ZIKV infection.

Methods: We developed quantitative frameworks to compare and explore infectome, diseasome, and comorbidity of ZIKV infections. We analyzed gene expression microarray and RNA-Seq data from ZIKV, West Nile fever (WNF), chikungunya, dengue, yellow fever, Japanese encephalitis virus, GBS, and control datasets. Using neighborhood-based benchmarking and multilayer network topology, we constructed relationship networks based on the Online Mendelian Inheritance in Man database and our identified significant genes.

Results: ZIKV infections showed dysregulation in expression of 929 genes. Forty-seven genes were highly expressed in both ZIKV and dengue infections. However, ZIKV shared <15 significant transcripts with other flavivirus infections. Notably, dysregulation of MAFB and SELENBP1 was common to ZIKV, dengue, and GBS infection; ATF5, TNFAIP3, and BAMB1 were common to ZIKV, dengue, and WNF; and NAMPT and PMAlP1 were common to ZIKV, GBS, and WNF. Phylogenetic, ontologic, and pathway analyses showed that ZIKV infection most resembles dengue fever.

Conclusions: We have developed methodologies to investigate disease mechanisms and predictions for infectome, diseasome, and comorbidities quantitatively, and identified particular similarities between ZIKV and dengue infections.

Keywords: Co-infections; Comorbidities; Diseasome; Genetic profiling; Zika Infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Comorbidity*
  • Gene Expression Profiling*
  • Gene Expression Regulation
  • Gene Ontology
  • Host-Pathogen Interactions / genetics*
  • Humans
  • Phylogeny
  • RNA Virus Infections / classification
  • RNA Virus Infections / diagnosis*
  • RNA Viruses / classification
  • RNA Viruses / genetics
  • RNA Viruses / isolation & purification
  • Sequence Analysis, RNA
  • Zika Virus / genetics
  • Zika Virus / isolation & purification*
  • Zika Virus Infection / diagnosis*