Tumor necrosis factor receptor expression and signal transduction in HIV-1-infected cells.
OBJECTIVE
To examine the inter-relationship between HIV-1 infection and the cell surface receptors for tumor necrosis factor (TNF)-alpha, an immunoregulatory cytokine that can enhance HIV-1 replication.


METHODS
Infected promyelocytic and promonocytic cells were examined because they normally express both types of TNF receptors.


METHODS
TNF receptor surface expression was determined by specific monoclonal antibody recognition and flow cytometry, and signal transduction was detected by gel shift analysis. HIV-1 activation and expression was quantitated by reverse transcriptase assay.


RESULTS
In the OM-10.1 promyelocytic model of chronic infection, TNF-alpha-induced HIV-1 expression also resulted in a substantial increase in 75 kd TNF receptor (TR75) expression although 55 kD TNF receptor (TR55) levels were not dramatically altered. A series of uninfected parental HL-60 subclones all reduced TR75 surface expression in response to TNF-alpha treatment. Enhanced TR75 expression on OM-10.1 cells followed the same TNF-alpha-dose dependency as that observed for HIV-1 production. An increase in TR75 expression was also evident during the peak of an acute HIV-1 infection of HL-60 promyelocytes. Although TR55 expression was unaltered during TNF-alpha-induced HIV activation, this receptor was still involved in the viral activation process. Antibody cross-linking of TR55, in the absence of exogenous TNF-alpha, induced maximal HIV-1 expression, an up-modulation of surface TR75, and nuclear NF-kappa B activity in OM-10.1 cultures. Surprisingly, this was the case even when an antagonistic anti-TR55 antibody was used. Anti-TR55 antibody cross-linking in chronically infected U1 promonocytic cultures could only partially substitute for TNF-alpha-induced HIV-1 expression.


CONCLUSIONS
Our results demonstrated that HIV-1 infection can selectively influence the surface expression of TNF receptors, potentially influencing its own expression and altering normal immunoregulatory signal transduction.
Butera
S T
ST
Retrovirus Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia 30333.
Roberts
B D
BD
Leung
K
K
Nabel
G J
GJ
Folks
T M
TM
D002478:Cells, Cultured; D003432:Cross-Linking Reagents; D006098:Granulocytes / Q000378:metabolism; D015497:HIV-1 / Q000254:growth & development*; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000096:biosynthesis*; D018124:Receptors, Tumor Necrosis Factor; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014775:Virus Activation; D014779:Virus Replication
D003432:Cross-Linking Reagents; D016328:NF-kappa B; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha