Activation and suppression of herpes simplex virus in a human T lymphoid cell line.

Abstract

Abstract The T lymphoblastoid line, CEM, was persistently infected with herpes simplex virus type 1 (HSV-1 ) for over 500 days. Within the first 120 days of this infection, a 24-day interval spontaneously occurred during which virus or viral antigen production diminished to undetectable levels. During this silent period, samples of these cells were treated with phytohemagglutinin (PHA) or concanavalin A (Con A). Virus production was observed within 3 days after PHA treatment. In contrast, Con A-treated cells remained negative for infectious virus and viral antigens for an additional 40 days at which point they were treated with PHA. Virus production again ensued within 3 days. Con A treatment of the HSV-producer line produced a consistent but transient diminution in virus titer, averaging 79.9, 78.6, and 79.8% at 24, 48, and 72 hr, respectively. Treatment of the producer line with neutralizing antiserum resulted in a rapid elimination of detectable infectious virus by 72 hr. Antiserum treatments of ≤5 days were associated with subsequent return of productive infection while treatments ≤9 days were not. Although productive infection did not spontaneously return to cultures treated with antibody for 9 days, PHA addition at the time of antibody removal resulted in activation of latent virus. The ability to predictably suppress HSV expression with Con A or neutralizing antiserum and to activate virus with PHA may permit this system to serve as a model for studying the state of HSV DNA and the factors controlling its expression in productively and latently infected lymphoid cells.