Activation of measles virus from silently infected human lymphocytes

Lymphocytes were incubated with measles virus for 4 days in the absence of a lymphocyte stimulating agent. Such nonstimulated lymphocytes, infected with measles virus, did not express the virus antigens that are detectable by cytotoxic antibodies. Approximately 1 out of 5,000, or even fewer, of such lymphocytes produced virus as demonstrated by the infectious center assay; in the supernate only 10--100 infectious viruses per milliliter were detected. No virus structures could be observed by means of an electron microscope. However, such lymphocytes showed no reaction to phytohemagglutinin (PHA) in terms of DNA synthesis in a subsequent culture in the presence of antibodies against measles to prevent spreading of the infection to other cells. Although stimulation by PHA did not result in a significant increase in [3H]thymidine incorporation, measles virus was activated; 32 h after the addition of PHA nearly 80% of the cells were killed by measles virus antibodies and complement. The number of virus-producing cells increased to approximately 1 in 300 or more, and at 72 h the virus titer in the supernate had risen to 10(6) infectious particles per ml. This reactivation of measles virus was still obtained when PHA was added as late as 8 or more days after the initial infection.