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Effect of herpes simplex virus type 1 infection on cytokine gene expression in activated murine peritoneal
L Wu1, T K Eisenstein, P S Morahan
1Department of Microbiology and Immunology, Medical College of Pennsylvania, Philadelphia 19129.
Abstract:
The intrinsic resistance to herpes simplex virus type 1 (HSV-1) of murine peritoneal macrophages (PM phi) obtained after in vivo infection of different stimuli has been investigated and shown to vary depending on the state of M phi activation. Activation of M phi by C. parvum (CP-M phi) or by an avirulent strain of S. typhimurium (Sal-M phi) increased the permissiveness of M phi to HSV-1 infection as evidenced by increased HSV-1 immediate early (IE) gene expression, synthesis of IE proteins, and the degree of cytopathic effect. HSV-1 infection was also found to sharply reduce the level of IL-1-beta mRNA in CP-M phi) and Sal-M phi, and the level of IL-3 mRNA in infected Sal-M phi, as measured by northern blot hybridization. Barely detectable levels of IL-beta mRNA were found in Sal-M phi after infection with HSV-1 when the polymerase chain reaction (PCR) assay was used to confirm the reduction of IL-1-beta mRNA. These data suggest that HSV-1 infection can modulate gene expression of some cytokines in the activated M phi.
Insights
Murine macrophages (M phi) show varied resistance to herpes simplex virus type 1 (HSV-1) based on activation state. Activated M phi become more permissive to HSV-1, with altered cytokine gene expression.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Murine peritoneal macrophages (M phi) exhibit intrinsic resistance to herpes simplex virus type 1 (HSV-1).
- The level of M phi activation influences their susceptibility to viral infection.
- Understanding these interactions is crucial for host-pathogen dynamics.
Purpose of the Study:
- To investigate the intrinsic resistance of murine peritoneal macrophages to HSV-1.
- To determine how M phi activation state affects HSV-1 permissiveness and gene expression.
- To analyze the impact of HSV-1 infection on cytokine mRNA levels in activated M phi.
Main Methods:
- In vivo activation of M phi using Corynebacterium parvum (CP-M phi) or Salmonella typhimurium (Sal-M phi).
- Assessment of HSV-1 infection by measuring immediate early (IE) gene expression, IE protein synthesis, and cytopathic effects.
- Quantification of cytokine mRNA levels (IL-1 beta, IL-3) using Northern blot hybridization and Polymerase Chain Reaction (PCR).
Main Results:
- Activated M phi (CP-M phi, Sal-M phi) showed increased permissiveness to HSV-1 infection.
- HSV-1 infection significantly reduced IL-1 beta mRNA levels in both CP-M phi and Sal-M phi.
- IL-3 mRNA levels were also reduced in infected Sal-M phi, confirmed by PCR.
Conclusions:
- The activation state of murine peritoneal macrophages critically modulates their susceptibility to HSV-1.
- HSV-1 infection can downregulate the expression of specific cytokine genes, such as IL-1 beta and IL-3, in activated macrophages.
- These findings highlight the complex interplay between HSV-1 and the macrophage immune response.