- 作者: Laszlo Orosz; Eva Gallyas; Lajos Kemeny; Yvette Mandi; Andrea Facsko; Klara Megyeri
- 作者服務機構: Department of Medical Microbiology and Immunobiology, University of Szeged, Dom ter 10, H-6720 Szeged, Hungary
- 中文摘要: --
- 英文摘要:
Background: The transcription factor p63 plays a pivotal role in the development and maintenance of
epithelial tissues, including the ocular surface. In an effort to gain insight into the
pathogenesis of keratitis caused by HSV-1, we determined the expression patterns of the p63
and Bax proteins in the Staatens Seruminstitute Rabbit Cornea cell line (SIRC).
Methods: SIRC cells were infected with HSV-1 at various multiplicities and maintained for different
periods of time. Virus replication was measured by indirect immunofluorescence assay and
Western blot analysis. Cell viability was determined by MTT assay. The apoptotic response of
the infected cells was quantified by ELISA detecting the enrichment of nucleosomes in the
cytoplasm. Western blot analysis was used to determine the levels of p63 and Bax proteins.
Results: Indirect immunofluorescence assays and Western blot analyses demonstrated the presence of
HSV-1 glycoprotein D (gD) in the infected SIRC cell line, and the pattern of gD expression
was consistent with efficient viral replication. The results of MTT and ELISA assays showed
that HSV-1 elicited a strong cytopathic effect, and apoptosis played an important role in the
demise of the infected cells. Mock-infected SIRC cells displayed the constitutive expression
of DNp63α. The expressions of the Bax-β and TAp63γ isoforms were considerably increased,
whereas the level of DNp63α was decreased in the HSV-1-infected SIRC cells. Experiments
involving the use of acyclovir showed that viral DNA replication was necessary for the
accumulation of TAp63γ.
Conclusion: These data suggest that a direct, virus-mediated cytopathic effect may play an important role
in the pathogenic mechanism of herpetic keratitis. By disturbing the delicate balance between
the pro-survival DN and the pro-apoptotic TA isoforms, HSV-1 may cause profound
alterations in the viability of the ocular cells and in the tissue homeostasis of the ocular
surface. - 中文關鍵字: --
- 英文關鍵字: --