g(m1)-ganglioside and Cell-Transformation--Viral

Mice with severe combined immune deficiency (C.B-17 scid/scid [SCID mice]) lack functional B and T lymphocytes and are permissive for the growth of human xenografts. However, the development of functional NK cells is not affected by the scid mutation. Mouse NK cells express the surface glycolipid asialo GM1 and are implicated in the rejection of heterotransplanted cells. In the present study, we demonstrate that SCID mice treated with rabbit anti-asialo GM anti-serum (alpha-asialo GM1), for in vivo depletion of endogenous NK cell function, develop lethal Epstein-Barr virus (EBV)-induced lymphoproliferative disorders (EBV-LPD) at lower doses od inoculated EBV-transformed lymphoblastoid B cell lines (EBV-LCL) than untreated animals. Furthermore, at any given dose of EBV-LCL inoculated, EBV-LPD developed earlier and induced lethality sooner in alpha-asialo GM1-treated animals. We also demonstrate that SCID mice treated with alpha-asialo GM1 have reduction in the number of asialo GM1-expressing splenocytes. Moreover, splenic cell suspensions derived from alpha-asialo GM1-treated SCID mice show lower cytotoxicity against the mouse NK-sensitive cell line YAC-1 and human EBV-LCL than splenocytes obtained from untreated SCID mice.

Topics: Animals; Antibodies; B-Lymphocytes; Cell Transformation, Viral; Cytotoxicity, Immunologic; G(M1) Ganglioside; Herpesvirus 4, Human; Humans; In Vitro Techniques; Killer Cells, Natural; Lymphoproliferative Disorders; Mice; Mice, SCID; Rabbits; Spleen; Transplantation, Heterologous

To develop an experimental model of adult T-cell leukemia/lymphoma in small animals, severe combined immunodeficiency (SCID) mice treated with anti-asialo GM-1 antibody were inoculated with MT-2 cells, a cell line transformed by the human T-cell leukemia virus (HTLV-I). Three mice injected with 4 x 10(7) cells subcutaneously or intramuscularly developed tumors at or near inoculation sites. Immunofluorescent antibody (IFA) staining for HTLV-I structural protein, p19, revealed the specific antigen in the cytoplasm of most cells from tumors and the DNA signals of HTLV-I proviral DNA were also positive in cellular DNA by polymerase chain reaction assay with HTLV-I tax gene primers, SK43/SK44. The MT-2 cells did not invade in mouse organs.

Topics: Animals; Antibodies; Cell Line, Transformed; Cell Transformation, Viral; DNA, Neoplasm; Fluorescent Antibody Technique; G(M1) Ganglioside; Human T-lymphotropic virus 1; Humans; Leukemia, T-Cell; Lymphoma, T-Cell; Mice; Mice, SCID; Neoplasm Transplantation; Polymerase Chain Reaction; T-Lymphocytes; Transplantation, Heterologous

The principal neutralizing domain (PND) of Human Immunodeficiency Virus type 1 (HIV-1) is mapped to a 24-amino acid sequence located in the hypervariable V3 region of the viral envelope protein. The PND of HIV-1 isolates from infected individuals corresponds mostly to that of the HIV-1 MN strain. We found that a peptide designed from the PND of HIV-1 MN virus greatly enhanced viral infection, while a peptide-derived PND of HTLV-IIIB virus showed at least 10-fold less efficient activity; no such effect was exhibited by the other peptides tested, including one designed from the PND of HIV-1 RF strain. The observed enhancing effect occurred in the early steps of viral infection and was not strain-restricted as both MN- and IIIB-derived peptides increased heterologous virus expression, including that of the RF strain. The MN- and, to a lesser extent, IIIB-derived peptides also increased CD4 expression on the cell membrane and differentially inhibited CD4 down-regulation induced by the phorbol ester TPA and/or by the monosialoganglioside GM1; the peptides showing no viral infection enhancement had no such effects. These findings demonstrate that the viral enhancement observed took place through a CD4-dependent mechanism and suggest that the PND is involved in HIV-1 infection and spread.

Topics: Amino Acid Sequence; CD4 Antigens; Cell Line; Cell Transformation, Viral; Chloramphenicol O-Acetyltransferase; G(M1) Ganglioside; HIV-1; Humans; Molecular Sequence Data; Neutralization Tests; Peptides; Tetradecanoylphorbol Acetate; Viral Envelope Proteins; Virus Replication

Topics: Animals; Antibiotics, Antineoplastic; Antigen-Antibody Complex; Avidin; Biotin; Cell Line; Cell Survival; Cell Transformation, Viral; Dactinomycin; G(M1) Ganglioside; Immunodiffusion; Kirsten murine sarcoma virus; Leukemia L5178; Leukemia, Experimental; Liposomes; Mice; Phosphatidylethanolamines; Zinostatin

Topics: Adenylyl Cyclases; Animals; Binding Sites; Cell Line; Cell Membrane; Cell Transformation, Viral; Cholera Toxin; G(M1) Ganglioside; Gangliosides; Male; Rats; Stimulation, Chemical