In vitro growth inhibition of murine leukemia cells by antibody specific for the major envelope glycoprotein (gp71) of friend leukemia virus

Abstract

An in vitro complement (C')-independent growth cytostasis model is described in which the replication of Friend leukemia virus (FLV)-induced erythroleukemia cells (of the FLC-745 cell line) is inhibited by goat serum directed against the major FLV envelope glycoprotein, gp71. The cytostatic effect is reversible, with the degree of this reversibility dependent on both the concentration and duration of exposure to immune serum. The inhibitory factor in heat-activated goat anti-FLV gp71 (delta G alpha FLV gp71) serum has been identified as virus-specific IgG antibody, and F(ab')2 fragments of this antibody are highly effective in suppressing FLC-745 cell growth. Studies with various murine leukemia and lymphoma cell lines, as well as with a panel of antisera directed against various murine oncornaviruses or viral proteins, have demonstrated that antibodies reactive with the group or type determinants of FLV gp71 are capable of mediating cytostasis. Under conditions of antibody-mediated growth inhibition of FLC-745 cells, specific modulation of gp71 expression is followed by nonspecific modulation of H-2d antigen expression. In addition, considerable cell death occurs in cytostatic cultures which is accompanied by continued division (as measured by DNA synthesis) of a portion of the cell population. Cytofluorimetric analysis of nuclei from growth-inhibited FLC-745 cells demonstrates a diminution in the frequency of cells in the G2/M phase of the cell cycle. It is suggested that antibody-mediate FLC-745 cell growth inhibition operates via a blockade of the cell cycle which prevents most cells in the population from traversing G2/M. While these blocked cells appear to be subject to slow cytolysis by a C'-independent mechanism, a portion of the cells escape this blockade and continue to replicate, thus offsetting the death of the former cells to yield a relatively constant density of viable cells for at least 72-96 h of growth inhibition. The possible relevance of this in vitro phenomenon to in vivo passive therapy against FLV-induced disease with G alpha FLV gp71 and similar antisera is briefly considered.

Role of Antibodies in Controlling Viral Disease: Lessons from Experiments of Nature and Gene Knockouts

“…Consistent with this view, a human recombinant antibody prevented neuronal spread to epithelial cells in an in vitro model (48) and when administered to HSVinfected animals, the same antibody was found to strongly localize on HSV-infected nerve fibers and sensory neurons (69). Evidence that antibodies can decrease virus expression in in vitro paradigms has also been reported both for HSV (55) and for other neurotropic and nonneurotropic viruses (21,23,36,53,54). However, although topically applied antibody protected mice from vaginal transmission of HSV type 2 (89), the course of vaginal HSV shedding following primary infection of B-cell-deficient mice did not differ from that of normal control mice (17).…”

Localization of a Passively Transferred Human Recombinant Monoclonal Antibody to Herpes Simplex Virus Glycoprotein D to Infected Nerve Fibers and Sensory Neurons In Vivo

“…In other cases, specific antibodies seem to reduce or abolish virus expression in infected neurons. Evidence that antibodies can affect virus expression in in vitro paradigms has been presented for neurotropic and nonneurotropic viruses, including measles (8), vesicular stomatitis virus (26), and Friend leukemia virus (11). Passive immunization of nude mice infected intracerebrally with Theiler's murine encephalomyelitis virus results in reduced virus yields in the brain and variable degrees of recovery from the demyelinating lesions (3).…”