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Comparison of herpes simplex virus type 1 DNA replication and virus production in murine bone marrow-derived and
Abstract:
The mechanism of resistance of murine macrophages (M phi) to infection by herpes simplex virus type 1 (HSV-1) was examined. Infection of bone marrow-derived M phi (BMDM phi) and resident peritoneal M phi (Res-M phi) was compared with infection of permissive Vero cells. In contrast to HSV-1 infection in Vero cells, no infectious virus was produced from either M phi cell type. However, marked cytopathic effect (c.p.e.) was evident in BMDM phi at 48 h post-infection, while there was no c.p.e. at any time post-infection in the Res-M phi. Cloned EcoRI subgenomic fragments representing the entire HSV-1 genome were used as probes in DNA :DNA hybridization experiments to determine the viral genome content in the infected cell types. In Res-M phi, HSV-1 DNA was present at early times post-infection but declined rapidly. In BMDM phi, the virus genome was always detected and increased with time after infection. The results suggest that Res-M phi restrict HSV-1 production at a point prior to viral DNA synthesis, whereas the block in HSV production in BMDM phi occurs at a later stage in the viral replicative cycle.
Insights
Murine macrophages resist herpes simplex virus type 1 (HSV-1) infection. Resident macrophages block viral DNA synthesis, while bone marrow-derived macrophages allow viral DNA replication but inhibit infectious virus production.
Area of Science:
- Virology
- Immunology
- Cell Biology
Background:
- Macrophages play a critical role in innate immunity against viral infections.
- Herpes simplex virus type 1 (HSV-1) is a common human pathogen.
- Understanding macrophage resistance mechanisms is key to controlling viral spread.
Purpose of the Study:
- To elucidate the mechanism of resistance of murine macrophages to HSV-1 infection.
- To compare HSV-1 replication in different macrophage populations and permissive cells.
Main Methods:
- Infection of bone marrow-derived macrophages (BMDM phi) and resident peritoneal macrophages (Res-M phi) with HSV-1.
- Comparison with HSV-1 infection in permissive Vero cells.
- DNA:DNA hybridization using HSV-1 genomic fragments to assess viral DNA presence and replication.
Main Results:
- Neither BMDM phi nor Res-M phi produced infectious HSV-1, unlike Vero cells.
- BMDM phi exhibited cytopathic effect (c.p.e.) at 48 hours post-infection; Res-M phi showed no c.p.e.
- Res-M phi showed transient HSV-1 DNA that declined rapidly, suggesting an early block.
- BMDM phi consistently detected HSV-1 DNA, which increased over time, indicating a later block in the viral cycle.
Conclusions:
- Resident peritoneal macrophages restrict HSV-1 early in infection, prior to viral DNA synthesis.
- Bone marrow-derived macrophages permit HSV-1 DNA replication but block infectious virus production at a later stage.