Role of interferon in persistent infection of macrophages with herpes simplex virus.

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.