Tumour necrosis factor-alpha increases the sensitivity of human immunodeficiency virus (HIV)-infected monocytic U937 cells to the complement-dependent cytotoxicity of sera from HIV type 1-infected individuals; role of the gp120 protein.
Sera of 40 intravenous drug addicts [25 seropositive and 15 seronegative for human immunodeficiency virus (HIV)] were tested for the presence of cytotoxic antibodies against uninfected and HIV-infected monocytic U937 cells. Six of the 25 seropositive samples proved to be cytotoxic for HIV-infected target cells in the presence of complement. The pretreatment of HIV-infected U937 cells with tumour necrosis factor (TNF)-alpha (which enhances virus production in these cells) increased the detection of serum cytotoxicity and 60% of these sera became cytotoxic. The percentage lysis was also increased after the TNF-alpha treatment of the target cells (from 16.2 +/- 4.5 to 71.2 +/- 4.9). The complement-dependent cytotoxic activity of these sera was significantly reduced by pretreatment with recombinant HIV gp120 antigen. This reduction was dose-dependent in the majority of cases. Immunofluorescence studies suggested that the cytotoxic sera mainly interacted with the viral antigens localized on the membrane of HIV-infected TNF-treated U937 cells. Moreover, comparative Western blot analyses using cellular extracts from untreated and TNF-treated U937 cells showed that there was a positive correlation between the cytotoxic phenotype and the capacity of sera to recognize the gp120 protein in extracts from TNF-treated HIV-infected cells. These results suggest that in some circumstances endogenous TNF-alpha can be a protective factor because it can render persistently infected cells highly sensitive to complement-dependent serum cytotoxicity as a result of increased expression of the relevant viral antigen (gp120) on the cell membrane.
Szabò
B
B
Department of Virology, Istituto Superiore di Sanità, Rome, Italy.
Locardi
C
C
Lo Presti
E
E
Belardelli
F
F
Benedetto
A
A
D000163:Acquired Immunodeficiency Syndrome / Q000097:blood* / Q000276:immunology*; D003165:Complement System Proteins / Q000502:physiology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D006678:HIV / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology* / Q000494:pharmacology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D009000:Monocytes; D011994:Recombinant Proteins / Q000494:pharmacology; D012016:Reference Values; D019966:Substance-Related Disorders / Q000097:blood / Q000276:immunology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D015699:HIV Envelope Protein gp120; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D003165:Complement System Proteins