Effect of antibody to HIV-1 Tat protein on viral replication in vitro and progression of HIV-1 disease in vivo.
In HIV-1-infected cell cultures, a relatively low concentration (5 micrograms/ml) of monoclonal antibody (mAb) against HIV-1-transactivating Tat protein was an efficient inhibitor of HIV-1 replication both in HIV-1(IIIB)-infected Jurkat cell and peripheral blood mononuclear cell (PBMC) cultures and significantly reduced the expression of a Tat-responsive CAT-reporter construct in HIV-1(IIIB)-infected Jurkat cells. Anti-Tat mAb also caused a significant reduction and a consistent delay in HIV-1 replication when added to PBMCs from HIV-1-infected patients cocultivated with phytohemagglutinin (PHA)-stimulated normal PBMCs. These data indicate that an autocrine-paracrine loop sustained by extracellular Tat protein, which is actively released by HIV-1-infected cells, may affect HIV-1 replication in cell cultures in vitro. An inverse relationship between natural anti-Tat antibody levels and p24 antigenemia was demonstrated by retrospective analysis of serial serum samples obtained from 10 HIV-1-seropositive hemophiliac patients followed over a 7-9-year period. This datum points to a possible influence of anti-Tat antibody on the progression of HIV-1 disease in vivo. These findings have strong implications for Tat protein as a possible target for specific immunotherapy in HIV-1-infected patients.
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Institute of Microbiology, University of Bologna Medical School, St. Orsola General Hospital, Italy.
Furlini
G
G
Vignoli
M
M
Ramazzotti
E
E
Roderigo
G
G
De Rosa
V
V
Zauli
G
G
Lolli
S
S
Capitani
S
S
La Placa
M
M
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D002460:Cell Line; D002478:Cells, Cultured; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D018450:Disease Progression; D015696:Gene Products, tat / Q000276:immunology*; D015483:HIV Antibodies / Q000276:immunology / Q000494:pharmacology*; D016655:HIV Core Protein p24 / Q000276:immunology; D015658:HIV Infections / Q000150:complications / Q000276:immunology* / Q000503:physiopathology; D015497:HIV-1 / Q000276:immunology / Q000502:physiology*; D006467:Hemophilia A / Q000150:complications; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D012091:Repetitive Sequences, Nucleic Acid; D015533:Transcriptional Activation; D014162:Transfection; D014779:Virus Replication / Q000187:drug effects / Q000276:immunology; D054322:tat Gene Products, Human Immunodeficiency Virus
D000911:Antibodies, Monoclonal; D015696:Gene Products, tat; D015483:HIV Antibodies; D016655:HIV Core Protein p24; D054322:tat Gene Products, Human Immunodeficiency Virus; D015500:Chloramphenicol O-Acetyltransferase