Open AccessTumour necrosis factor- 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
Author(s) -
Béla Szabó,
C Locardi,
Elena Lo Presti,
Filippo Belardelli,
A. Benedetto
Publication year - 1993
Publication title -
journal of general virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.55
H-Index - 167
eISSN - 1465-2099
pISSN - 0022-1317
DOI - 10.1099/0022-1317-74-7-1271
Subject(s) - biology , virology , cytotoxicity , u937 cell , human immunodeficiency virus (hiv) , virus , immunology , tumor necrosis factor alpha , complement (music) , cell culture , in vitro , phenotype , biochemistry , genetics , complementation , gene
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.