Replication of many human viruses is refractory to inhibition by endogenous cellular MicroRNAs

Hal P. Bogerd, Rebecca L. Skalsky, Edward M. Kennedy, Yuki Furuse, Adam W. Whisnant, Omar Flores, Kimberly L W Schultz, Nicole Putnam, Nicholas J. Barrows, Barbara Sherry, Frank Scholle, Mariano A. Garcia-Blanco, Diane Griffin, Bryan R. Cullen

Research output: Contribution to journalArticle

Abstract

The issue of whether viruses are subject to restriction by endogenous microRNAs (miRNAs) and/or by virus-induced small interfering RNAs (siRNAs) in infected human somatic cells has been controversial. Here, we address this question in two ways. First, using deep sequencing, we demonstrate that infection of human cells by the RNA virus dengue virus (DENV) or West Nile virus (WNV) does not result in the production of any virus-derived siRNAs or viral miRNAs. Second, to more globally assess the potential of small regulatory RNAs to inhibit virus replication, we used gene editing to derive human cell lines that lack a functional Dicer enzyme and that therefore are unable to produce miRNAs or siRNAs. Infection of these cells with a wide range of viruses, including DENV, WNV, yellow fever virus, Sindbis virus, Venezuelan equine encephalitis virus, measles virus, influenza A virus, reovirus, vesicular stomatitis virus, human immunodeficiency virus type 1, or herpes simplex virus 1 (HSV-1), failed to reveal any enhancement in the replication of any of these viruses, although HSV-1, which encodes at least eight Dicer-dependent viral miRNAs, did replicate somewhat more slowly in the absence of Dicer. We conclude that most, and perhaps all, human viruses have evolved to be resistant to inhibition by endogenous human miRNAs during productive replication and that dependence on a cellular miRNA, as seen with hepatitis C virus, is rare. How viruses have evolved to avoid inhibition by endogenous cellular miRNAs, which are generally highly conserved during metazoan evolution, remains to be determined.

Original languageEnglish (US)
Pages (from-to)8065-8076
Number of pages12
JournalJournal of Virology
Volume88
Issue number14
DOIs
StatePublished - 2014

Fingerprint

vertebrate viruses
MicroRNAs
microRNA
Viruses
viruses
small interfering RNA
Small Interfering RNA
Human herpesvirus 1
West Nile virus
Dengue virus
Dengue Virus
Human Herpesvirus 1
Virus Replication
Yellow fever virus
Venezuelan Equine Encephalitis Viruses
Sindbis virus
Venezuelan equine encephalitis virus
Ribonuclease III
Sindbis Virus
Measles virus

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Bogerd, H. P., Skalsky, R. L., Kennedy, E. M., Furuse, Y., Whisnant, A. W., Flores, O., ... Cullen, B. R. (2014). Replication of many human viruses is refractory to inhibition by endogenous cellular MicroRNAs. Journal of Virology, 88(14), 8065-8076. https://doi.org/10.1128/JVI.00985-14

Replication of many human viruses is refractory to inhibition by endogenous cellular MicroRNAs. / Bogerd, Hal P.; Skalsky, Rebecca L.; Kennedy, Edward M.; Furuse, Yuki; Whisnant, Adam W.; Flores, Omar; Schultz, Kimberly L W; Putnam, Nicole; Barrows, Nicholas J.; Sherry, Barbara; Scholle, Frank; Garcia-Blanco, Mariano A.; Griffin, Diane; Cullen, Bryan R.

In: Journal of Virology, Vol. 88, No. 14, 2014, p. 8065-8076.

Research output: Contribution to journalArticle

Bogerd, HP, Skalsky, RL, Kennedy, EM, Furuse, Y, Whisnant, AW, Flores, O, Schultz, KLW, Putnam, N, Barrows, NJ, Sherry, B, Scholle, F, Garcia-Blanco, MA, Griffin, D & Cullen, BR 2014, 'Replication of many human viruses is refractory to inhibition by endogenous cellular MicroRNAs', Journal of Virology, vol. 88, no. 14, pp. 8065-8076. https://doi.org/10.1128/JVI.00985-14
Bogerd HP, Skalsky RL, Kennedy EM, Furuse Y, Whisnant AW, Flores O et al. Replication of many human viruses is refractory to inhibition by endogenous cellular MicroRNAs. Journal of Virology. 2014;88(14):8065-8076. https://doi.org/10.1128/JVI.00985-14
Bogerd, Hal P. ; Skalsky, Rebecca L. ; Kennedy, Edward M. ; Furuse, Yuki ; Whisnant, Adam W. ; Flores, Omar ; Schultz, Kimberly L W ; Putnam, Nicole ; Barrows, Nicholas J. ; Sherry, Barbara ; Scholle, Frank ; Garcia-Blanco, Mariano A. ; Griffin, Diane ; Cullen, Bryan R. / Replication of many human viruses is refractory to inhibition by endogenous cellular MicroRNAs. In: Journal of Virology. 2014 ; Vol. 88, No. 14. pp. 8065-8076.
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