Similarity in viral and host promoters couples viral reactivation with host cell migration

Kathrin Bohn-Wippert, Erin N. Tevonian, Melina R. Megaridis, Roy David Dar

Research output: Contribution to journalArticle

Abstract

Viral-host interactomes map the complex architecture of an evolved arms race during host cell invasion. mRNA and protein interactomes reveal elaborate targeting schemes, yet evidence is lacking for genetic coupling that results in the co-regulation of promoters. Here we compare viral and human promoter sequences and expression to test whether genetic coupling exists and investigate its phenotypic consequences. We show that viral-host co-evolution is imprinted within promoter gene sequences before transcript or protein interactions. Co-regulation of human immunodeficiency virus (HIV) and human C-X-C chemokine receptor-4 (CXCR4) facilitates migration of infected cells. Upon infection, HIV can actively replicate or remain dormant. Migrating infected cells reactivate from dormancy more than non-migrating cells and exhibit differential migration-reactivation responses to drugs. Cells producing virus pose a risk for reinitiating infection within niches inaccessible to drugs, and tuning viral control of migration and reactivation improves strategies to eliminate latent HIV. Viral-host genetic coupling establishes a mechanism for synchronizing transcription and guiding potential therapies.

Original languageEnglish (US)
Article number15006
JournalNature communications
Volume8
DOIs
StatePublished - Jan 1 2017

Fingerprint

Viruses
Cell Movement
human immunodeficiency virus
HIV
cells
infectious diseases
CXC Chemokines
drugs
Chemokine Receptors
proteins
Transcription
Infection
Pharmaceutical Preparations
viruses
Proteins
Tuning
Genes
genes
therapy
Messenger RNA

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Similarity in viral and host promoters couples viral reactivation with host cell migration. / Bohn-Wippert, Kathrin; Tevonian, Erin N.; Megaridis, Melina R.; Dar, Roy David.

In: Nature communications, Vol. 8, 15006, 01.01.2017.

Research output: Contribution to journalArticle

Bohn-Wippert, Kathrin ; Tevonian, Erin N. ; Megaridis, Melina R. ; Dar, Roy David. / Similarity in viral and host promoters couples viral reactivation with host cell migration. In: Nature communications. 2017 ; Vol. 8.
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