Persistent elevated expression of cytokine transcripts in ganglia latentlyinfected with herpes simplex virus in the absence of ganglionic replication or reactivation

Infection of mouse trigeminal ganglia by herpes simplex virus induces cytok ine expression that persists long after infectious virus or viral antigens become undetectable. To examine mechanisms underlying this phenomenon, we u sed a thymidine kinase mutant, d/sptk, which fails to replicate in ganglia and does not reactivate upon ganglionic explant. Using quantitative reverse transcriptase-polymerase chain reaction assays, we found that levels of in terferon-gamma and tumor necrosis factor-alpha transcripts in d/sptk-infect ed ganglia were lower than those in wild type-infected ganglia, but were si gnificantly (eight- to 10-fold) higher than those in mock-infected ganglia from Day 3 to Day 100 postinfection. We also studied latency-associated tra nscript (LAT) negative mutants that exhibit increased expression of product ive cycle transcripts in ganglia. Ganglia infected with these mutants conta ined levels of cytokine transcripts similar to those in wild type-infected ganglia; any increases in Viral antigen expression mediated by the LAT dele tion were not accompanied by increased cytokine expression. Thus, neither v iral replication, the ability to reactivate, nor LAT expression in ganglia is required for persistent elevated cytokine expression. The results provid e indirect evidence that low-level expression of viral productive cycle gen es in neurons can provide signals that elicit cytokine expression. (C) 2000 Academic Press.