Herpesvirus-encoded microRNAs detected in human gingiva alter host cell transcriptome and regulate viral infection

Afsar R. Naqvi*, Alexandra Seal, Jennifer Shango, Maria F. Brambila, Gloria Martinez, Gabriela Chapa, Shirin Hasan, Tejabhiram Yadavalli, Dinesh Jaishankar, Deepak Shukla, Salvador Nares

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


MicroRNAs (miRNAs) are small, non-coding RNAs of ~18–25 nucleotides that have gained extensive attention as critical regulators in complex gene networks including immune cell lineage commitment, differentiation, maturation, and maintenance of immune homeostasis and function. Many viruses encode miRNAs that directly downregulate the expression of factors of the innate immune system, which includes proteins involved in promoting apoptosis and recruitment. In this study, we examined the expression profiles of three previously identified viral miRNAs (v-miRs) from the human herpesvirus (HHV) family, HSV-1 (miR-H1), KSHV (miR-K12-3-3p), and HCMV (miR-US4) in healthy and diseased periodontal tissues and observed increased levels of v-miRs in diseased tissues. To understand the significance of this increase, we overexpressed v-miRs in human oral keratinocytes (HOK), a common target for various HHV, and analyzed the impact of miR-H1 and miR-K12-3-3p on the host transcriptome. More than 1300 genes were altered in HOK overexpressing miR-H1 and miR-K12-3-3p. Global pathway analysis of deregulated genes identified several key cellular pathways that may favor viral persistence. Using bioinformatic analysis, we predicted hundreds of potential v-miR binding sites on genes downregulated by miR-H1 and miR-K12-3-3p and validated three novel target v-miR sites suggesting widespread direct and indirect modulation of numerous host genes/pathways by a single v-miR. Finally, in vitro HSV-1 infection assays showed that miR-H1 can regulate viral entry and infection in human oral keratinocytes (HOK). Overall, our results demonstrate clinical and functional relevance of pathogenic viral molecules viz., v-miRs that regulate both host and viral functions and may contribute to the pathogenesis of inflammatory oral diseases.

Original languageEnglish (US)
Pages (from-to)497-508
Number of pages12
JournalBiochimica et Biophysica Acta - Gene Regulatory Mechanisms
Issue number5
StatePublished - May 2018
Externally publishedYes


  • Gingival keratinocytes
  • HSV-1
  • Herpesvirus
  • Inflammation
  • Transcriptome
  • Viral microRNA

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics


Dive into the research topics of 'Herpesvirus-encoded microRNAs detected in human gingiva alter host cell transcriptome and regulate viral infection'. Together they form a unique fingerprint.

Cite this