Summary auto-generated
This study demonstrates that herpes simplex virus type 1 (HSV-1) infection of human fibroblasts activates cellular interferon-responsive genes, similar to cytomegalovirus (HCMV) infection. Five genes tested—ISG54, IFI56, ISG15, 9-27, and MxA—were activated following HSV-1 infection. Notably, this activation occurred without new viral protein synthesis, indicating that virion components alone trigger the response. The induction required neither the JAK-STAT signaling pathway nor soluble interferon, as demonstrated using cell lines lacking JAK1, STAT1, or Tyk2. Instead, HSV-1 appears to activate an alternative pathway, possibly through interaction of viral glycoproteins with cellular receptors. However, during normal infection without cycloheximide treatment, ISG54 induction was not observed, suggesting HSV-1 encodes factors that suppress this interferon response. The study clarifies earlier conflicting reports and reveals that HSV-1, though less potent than HCMV, can directly activate interferon-responsive gene expression through mechanisms distinct from interferon-α signaling.
Key findings
- HSV-1 infection activates expression of five interferon-responsive genes (ISG54, IFI56, ISG15, 9-27, MxA) without requiring viral protein synthesis
- HSV-1-mediated induction bypasses the JAK-STAT pathway, operating independently of the interferon-α signaling mechanism
- Viral particle binding or virion components within infected cells are sufficient to trigger interferon-responsive gene activation
- HSV-1 is a less efficient inducer than HCMV, suggesting differences in viral mechanisms of immune evasion
- Wild-type HSV-1 normally suppresses interferon-responsive gene expression during active infection, indicating the virus encodes antagonistic functions
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Abstract
Previous studies have shown that infection of human fibroblasts with human cytomegalovirus (HCMV) results in activation of cellular interferon-responsive gene expression. We demonstrate here that infection of human fibroblasts with herpes simplex virus type 1 (HSV-1) in the absence of de novo protein synthesis also induces the expression of interferon-responsive genes. Five genes tested (encoding ISG54, IFI56, ISG15, 9-27 and MxA) were activated by infection with HSV-1, although the degree of response varied between the individual genes. HSV-1 was a less efficient inducer than HCMV. The effect was a consequence of binding of the virus particle to the cell surface or of the presence of virion components within the infected cell. Induction was mediated by a pathway other than the mechanism through which interferon-α mediates its effects on cellular gene expression.