Important note: Information in this article was accurate in 1988. The state of the art may have changed since the publication date.
VACCINIA/AIDS RECOMBINANT VIRUS: EVIDENCE FOR SHEDDING OF GP120 (ENV) FROM THE CELL SURFACE
Vaccines 87. Modern Approaches to New Vaccines: Prevention of AIDS and Other Viral, Bacterial, and Parasitic Diseases. Chanock RM et al, eds. New York, Cold Spring Harbor Laboratory, p. 242-9, 1987.. Unique Identifier : AIDSLINE ICDB/88647985 Kieny MP; Rautmann G; Lecocq JP; Wain-Hobson S; Montagnier L; Girard M; Transgene S.A., 67000 Strasbourg, France
Abstract:
The human immunodeficiency virus (HIV), a novel retrovirus, is now recognized as the causative agent of acquired immune deficiency syndrome (AIDS). HIV exhibits a characteristic tropism for T4 lymphocytes, although both macrophages and neural tissue can also be infected. AIDS patients (pts) suffer from severe immunosuppression due to loss of T4 helper cells and consequently are vulnerable to opportunistic infections. In addition to the gag, pol, and env genes, HIV encodes additional functions termed TAT, ART, Q/sor, and F/3'orf. The retrovirus envelope glycoprotein is classically exposed at the surface of the viral particle, and the env gene of HIV affords an obvious target for the engineering of a vaccine against AIDS. Vaccinia virus, an orthopoxvirus related to cowpox, although not completely innocuous, has long been considered safe for human use. Vaccinia virus was used for construction of a vaccine against HIV and to express the env-coding sequence. The recombinant vaccinia virus bearing the HIV (lymphadenopathy-associated virus [LAV] isolate) env-coding sequence determines the synthesis of an env protein that is specifically recognized by sera from AIDS pts. As with the authentic HIV envelope glycoprotein, the primary translation product gp160 is cleaved in vivo to generate gp120 and gp40. Mice inoculated with the recombinant, however, develop only low titers of circulating antibodies capable of recognizing isolated env proteins of HIV. The env glycoprotein is shed from the cell surface into the culture medium as early as 4 hr after labeling. Low immunogenicity of the recombinant may be related to lability of gp120 attachment to the surface of the infected cell. It has been reported that secreted proteins are strongly diminished in their ability to elicit neutralizing antibody and, in addition, circulating gp120-env has the potential to exert a direct influence on the immune system of the host through an interaction with T lymphocytes. (47 Refs)
Keywords: Acquired Immunodeficiency Syndrome/*IMMUNOLOGY Animal Antibodies, Viral/ANALYSIS Cell Line Human HIV/GENETICS/*IMMUNOLOGY Mice Mice, Inbred Strains *Recombination, Genetic Retroviridae Proteins/*IMMUNOLOGY Vaccines, Synthetic/IMMUNOLOGY Vaccinia Virus/GENETICS/*IMMUNOLOGY MEETING PAPER
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Important note: Information in this article was accurate in 1988. The state of the art may have changed since the publication date.
