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Role of interferon in persistent infection of macrophages with herpes simplex virus
Abstract:
Splenic macrophage cultures from C57BL/6 mice resistant to infection with herpes simplex virus (HSV) in vivo survived HSV infection in vitro. In contrast, macrophages from HSV-susceptible DBA/2 mice were completely lysed by the virus. During prolonged culturing, macrophages from C57BL/6 mice continued to produce infectious virus, indicating establishment of a persistent infection. At this time, interferon (IFN) was undetectable. However, as shown directly by the addition of an anti-IFN serum and indirectly by an increased activity of (2'-5')oligoadenylate synthetase, IFN was involved in the maintenance of the persistent infection. During the acute phase of virus infection, viral DNA replication was identical in macrophages from resistant or susceptible mice. Later, viral DNA content and the number of cells expressing HSV antigens decreased in macrophages from C57BL/6 mice. However, single cells remained to express viral proteins and to produce infectious particles. The results show that macrophages can be persistently infected with HSV due to their genetically controlled properties.
Insights
Macrophages from resistant mice can harbor persistent herpes simplex virus (HSV) infections, with interferon (IFN) playing a role in maintaining the infection. This highlights genetically controlled macrophage properties in HSV persistence.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Herpes simplex virus (HSV) infection outcomes vary significantly between mouse strains.
- Macrophages play a crucial role in the immune response to viral infections.
Purpose of the Study:
- To investigate the susceptibility of splenic macrophages from different mouse strains to HSV infection.
- To elucidate the mechanisms underlying persistent HSV infection in macrophages.
Main Methods:
- In vitro culture of splenic macrophages from C57BL/6 (resistant) and DBA/2 (susceptible) mice.
- Infection of macrophage cultures with HSV.
- Assessment of viral DNA replication, viral antigen expression, and infectious virus production.
- Interferon (IFN) involvement was studied using anti-IFN serum and (2'-5')oligoadenylate synthetase activity.
Main Results:
- Macrophages from resistant C57BL/6 mice survived HSV infection in vitro, establishing persistent infections with infectious virus production.
- Macrophages from susceptible DBA/2 mice were lysed by HSV.
- Interferon (IFN) was found to be involved in maintaining the persistent HSV infection in C57BL/6 macrophages.
- While viral DNA replication was initially similar, later stages showed decreased viral DNA and antigen expression in C57BL/6 macrophages, with some cells retaining viral protein expression and particle production.
Conclusions:
- Macrophages possess genetically determined properties that allow for persistent herpes simplex virus (HSV) infection.
- Interferon (IFN) is implicated in the maintenance of HSV persistence within macrophages.
- Macrophage susceptibility and response to HSV are influenced by host genetic factors.