Activation of measles virus from silently infected human lymphocytes.

Abstract

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.

Measles Virus Persistence in Human Lymphocytes: A Role for Virus-induced Interferon

“…The ability of measles virus to persist in unstimulated human PBLs has been described in numerous reports (Joseph et al, 1975, Sullivan et al, 1975Lucas et al, 1978b). In all instances, stimulation of these cells by plant mitogens (phytohaemaggltltinin, concanavalin A, PWM) or allogeneic lymphocytes resulted in productive measles virus infection (Sullivan et al, 1975).…”

“…Only one report (Lucas et al, 1978b) has measured the production of interferon in lymphocytes infected with measles virus with and without mitogen stimulation (phytohaemagg-lutinin). In this study, only small amounts of interferon were detected in either infected or uninfected mitogen-stimulated cultures.…”

“…Infection of normal, resting lymphocytes resulted in a 'silent' infection in which small amounts of infectious virus were produced and no significant expression of virus antigens on cell membranes occurred (Lucas et al, 1978a;Joseph et al, 1975). The apparent block of measles virus replication in these 'silently' infected human lymphocytes was overcome by the addition of mitogen (Lucas et al, 1978b).…”

Growth of Measles Virus in Epithelial and Lymphoid Tissues of Cynomolgus Monkeys

“…Such restricted growth of measles virus in the lymphoid cells has been indicated by several investigators (2,3,6,11). Whether the restricted production of H and F proteins in the lymphoid cells is relevant to the apparent lack of virus growth remains for future study.…”

Comparative Aspects of Pathogenicity of Measles, Canine Distemper, and Rinderpest Viruses

“…In vitro studies indicate that MV can grow in lymphoblastoid cell lines of both T and B cell types (Joseph, Lampert and Oldstone, 1975;Sullivan et al, 1975;Barry et al, 1976;Minagawa et al, 1976;Minagawa and Sakuma, 1977). In small lymphocytes, MV is thought to exist in a silent state that can be activated to pro duce mature virus in lymphoblastoid cells (Osunkoya et al, 1974a,b;Lucas et al, 1978). Virus-infected small lymphocytes may carry the virus to various parts of the body particularly to the epithelial tissues and the brain.…”