Modulation of Immune System Function by Measles Virus Infection. II. Infection of B Cells Leads to the Production of a Soluble Factor That Arrests Uninfected B Cells in G 0 /G 1

Abstract

Measles can result in a variety of immunologic defects. Previously we showed that an Epstein-Barr virus-transformed B cell line (B cells), when infected with measles virus, produced a soluble antiproliferative factor that inhibited proliferation of T and B cells. Here we explore the effects of infection by measles virus versus the virus-free soluble antiproliferative factor on B cells. The B cells showed no change in the amounts of interleukin (IL)-2, 10, 12, interferon (IFN)-γ, or transforming growth factor (TGF)-β when infected or exposed to the soluble factor. Similarly, B cells showed no change in the expression of class II major histocompatibility antigens, LFA-1, ICAM-1, CD19, CD40, CD80, CD86, CD95 (Fas), or CD178 (FasL). Cell cycle analysis showed that measles virus infection caused an accumulation of cells in S and G₂/M phases with a "sub-G₁" cell population, while incubation of cells with the soluble factor caused an accumulation in G₀/G₁. These experiments provide evidence that measles virus causes a profound inhibition of B cell proliferation without distinguishable changes in cytokine profile or cell surface phenotype. Further, it appears that there are two populations of cells affected by infection: one population is growth arrested due to the influence of the immunosuppressive factor and is not infected; a second population that is infected progresses through S phase less efficiently. Alternatively, while both the soluble factor and live virus infection may affect cells in G₀/G₁ phases, only live virus infection could selectively induce apoptosis of G₀/G₁ cells, resulting in cell accumulation in S and G₂/M phases with a build up of "sub-G₁" cells.