Production of interferon in human diploid cells at different population doubling levels

Komatsu, H.; Maehara, Nobutoshi; Shimoda, K.; Mōri, Takayuki; Lee, T.; Makino, Satoshi; Matumoto, Minoru

doi:10.1007/bf01320251

Cited by 3 publications

(1 citation statement)

References 9 publications

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“…In the current study, primary human dermal fibroblasts (HDFs) derived from neonatal foreskin explants were used to further investigate the contribution of type I IFN to MV host range and cell tropism. Neonatal HDFs initially exhibit decreased basal level IFN activity following explantation that increases with progressive population doublings (PD) as cells are passaged in vitro, a process commonly used as a model for cellular aging and the progression toward senescence (Komatsu et al, 1981;St. Geme and Horrigan, 1969).…”

Section: Introductionmentioning

confidence: 99%

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

Johnston

Nazarian

Natale³

et al. 2005

Virology

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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-beta, but not IFN-alpha, 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.

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Section: Introductionmentioning

confidence: 99%