Stimulation of Macrophages by Endotoxin Results in the Reactivation of a Persistent Herpes Simplex Virus Infection

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Abstract
Previous work has shown that splenic macrophages derived from herpes simplex virus (HSV)-resistant C57BL/6 mice undergo a persistent HSV infection which is characterized by the continuous release of infectious virus particles from a small subpopulation of infected cells. Treatment of persistently infected macrophages for 2 weeks with lipopolysaccharide (LPS) resulted in an increase of HSV yield and in virus-induced cytopathic effects. HSV was also reactivated by treatment of macrophage cultures with lipid A or tumour necrosis factor (TNF). Like macrophages of C57BL/6 origin, cells from LPS-hyporesponsive C3H/HeJ mice could be persistently infected with HSV. These cells were resistant to LPS-induced virus reactivation. The results show that macrophages derived from C57BL/6 mice are rendered susceptible to lytic HSV infection by treatment with LPS or TNF. Thus, these substances may interfere with persistent HSV infection which can be established due to genetically controlled properties of the host.