Myxoma virus infection of primary human fibroblasts varies with cellular age and is regulated by host interferon responses

J. B. Johnston, Steven H. Nazarian, Renato Natale, Douglas McFadden

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Recent studies have indicated a critical role for interferon (IFN)-mediated antiviral responses in the host range of myxoma virus (MV), a pathogenic poxvirus of rabbits. To investigate the contribution of IFN to MV tropism in nonleporine cells, primary human dermal fibroblasts (HDFs) were tested for permissiveness to MV infection. Low-passage HDFs that underwent fewer than 25 population doublings (PD) were fully permissive for MV infection, supporting productive virus replication and cell-to-cell spread. In contrast, early and late viral gene expression was detectable in high-passage HDF (>75 PD), but MV failed to generate infectious progeny and could not form foci in these cells. Vesicular stomatitis virus (VSV) plaque reduction assays confirmed that constitutive IFN production progressively increased as HDFs were passaged, concurrent with an increase in the expression of transcripts for type I IFN and IFN-responsive genes involved in antiviral responses. These findings correlated with the enhanced sensitivity of higher-passage HDF to inducers of type I IFN responses, such as dsRNA. Furthermore, pretreatment of low-passage HDF with type I IFN abrogated MV spread and replication while treatment of mature HDF with neutralizing antibodies to IFN-β, but not IFN-α, restored the capacity to form foci. These findings emphasize the importance of post-entry events in determining the permissiveness of human cells to MV infection and support a critical role for innate type I IFN responses as key determinants of poxvirus host range and species restriction.

Original languageEnglish (US)
Pages (from-to)235-248
Number of pages14
JournalVirology
Volume332
Issue number1
DOIs
StatePublished - Feb 5 2005
Externally publishedYes

Fingerprint

Myxoma virus
Virus Diseases
Interferons
Fibroblasts
Interferon Type I
Skin
Permissiveness
Poxviridae
Host Specificity
Virus Replication
Antiviral Agents
Vesicular Stomatitis
Tropism
Viral Genes
Neutralizing Antibodies
Population
Rabbits
Viruses
Gene Expression

Keywords

  • Antiviral responses
  • Host range
  • Interferon
  • Myxoma virus
  • Poxvirus
  • Tropism

ASJC Scopus subject areas

  • Virology

Cite this

Myxoma virus infection of primary human fibroblasts varies with cellular age and is regulated by host interferon responses. / Johnston, J. B.; Nazarian, Steven H.; Natale, Renato; McFadden, Douglas.

In: Virology, Vol. 332, No. 1, 05.02.2005, p. 235-248.

Research output: Contribution to journalArticle

Johnston, J. B. ; Nazarian, Steven H. ; Natale, Renato ; McFadden, Douglas. / Myxoma virus infection of primary human fibroblasts varies with cellular age and is regulated by host interferon responses. In: Virology. 2005 ; Vol. 332, No. 1. pp. 235-248.
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