Tumor necrosis factor-alpha drives HIV-1 replication in U937 cell clones and upregulates CXCR4.

U937 cell clones in which efficient (plus) vs poor (minus) replication of HIV-1 occurs have been described. We evaluated the role of host factors in their differential ability to support HIV-1 replication. Plus clones constitutively produced TNF-alpha and viral replication was inhibited by neutralization of endogenous TNF-alpha. However, HIV-1 replication was strongly upregulated in minus clones by exogenous TNF-alpha, which also further accelerated the kinetics of infection in plus clones. We observed an increased accumulation of proviral DNA within one round of HIV-1 replication following TNF-a treatment of plus cells. This effect was associated with increased surface density of CXCR4 in both plus and minus clones. Our results identify TNF-alpha as one correlate that contributes to the higher ability of U937-plus clones to sustain HIV-1 replication. Furthermore, we suggest that TNF-alpha may affect steps of the viral life cycle that occur earlier than transcription and also enhance HIV-1 replication by increasing the surface density of CXCR4.

[1]  E. Vicenzi,et al.  Envelope-Dependent Restriction of Human Immunodeficiency Virus Type 1 Spreading in CD4+ T Lymphocytes: R5 but Not X4 Viruses Replicate in the Absence of T-Cell Receptor Restimulation , 1999, Journal of Virology.

[2]  M. Mengozzi,et al.  1,25-Dihydroxyvitamin D3 Upregulates Functional CXCR4 Human Immunodeficiency Virus Type 1 Coreceptors in U937 Minus Clones: NF-κB-Independent Enhancement of Viral Replication , 1998, Journal of Virology.

[3]  H. Augustin,et al.  Endothelial cells differentially express functional CXC-chemokine receptor-4 (CXCR-4/fusin) under the control of autocrine activity and exogenous cytokines. , 1998, Biochemical and biophysical research communications.

[4]  P. Pitha,et al.  Interferon downregulates CXCR4 (fusin) gene expression in peripheral blood mononuclear cells. , 1998, Journal of human virology.

[5]  Roberts Bd,et al.  Changes in CXC-chemokine receptor-4 expression during HIV-1 replication are independent of CD4 modulations. , 1997 .

[6]  J. Hoxie,et al.  Promonocytic U937 subclones expressing CD4 and CXCR4 are resistant to infection with and cell-to-cell fusion by T-cell-tropic human immunodeficiency virus type 1 , 1997, Journal of virology.

[7]  A. Fauci,et al.  Cloning and analysis of the promoter region of CXCR4, a coreceptor for HIV-1 entry. , 1997, Journal of immunology.

[8]  A. Fauci,et al.  HIV replication in IL-2-stimulated peripheral blood mononuclear cells is driven in an autocrine/paracrine manner by endogenous cytokines. , 1995, Journal of immunology.

[9]  A. Fauci,et al.  A family of serine proteases expressed exclusively in myelo-monocytic cells specifically processes the nuclear factor-kappa B subunit p65 in vitro and may impair human immunodeficiency virus replication in these cells , 1994, The Journal of experimental medicine.

[10]  A. Fauci,et al.  Cytokine modulation of HIV expression. , 1993, Seminars in immunology.

[11]  M. Wainberg,et al.  Differential susceptibilities of U-937 cell clones to infection by human immunodeficiency virus type 1 , 1992, Journal of virology.

[12]  C. Dieffenbach,et al.  Increased human immunodeficiency virus (HIV) expression in chronically infected U937 cells upon in vitro differentiation by hydroxyvitamin D3: roles of interferon and tumor necrosis factor in regulation of HIV production , 1990, Journal of virology.

[13]  J. Mellors,et al.  Tumor necrosis factor-alpha/cachectin enhances human immunodeficiency virus type 1 replication in primary macrophages. , 1991, The Journal of infectious diseases.

[14]  E. Fenyö,et al.  Susceptibility to infection by the human immunodeficiency virus (HIV) correlates with T4 expression in a parental monocytoid cell line and its subclones. , 1987, Virology.