TUMOR NECROSIS FACTOR-α DRIVES HIV-1 REPLICATION IN U937 CELL CLONES AND UPREGULATES CXCR4

• Published in: Cytokine (Philadelphia, Pa.) Pa.), 2001-01, Vol.13 (1), p.55-59
• Main Authors: Biswas, Priscilla, Mantelli, Barbara, Delfanti, Fanny, Cota, Manuela, Vallanti, Giuliana, de Filippi, Camilla, Mengozzi, Manuela, Vicenzi, E., Lazzarin, A., Poli, Guido
• Format: Article
• Language: English
• Subjects: Base Sequence; Chemokine CXCL12; Chemokines, CXC - genetics; CXCR4/HIV-1/U937/TNF-α; DNA Primers - genetics; HIV-1 - drug effects; HIV-1 - growth & development; HIV-1 - physiology; Humans; NF-kappa B - metabolism; Receptors, CXCR4 - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - pharmacology; Tumor Necrosis Factor-alpha - physiology; U937 Cells; Up-Regulation - drug effects; Virus Replication - drug effects; Virus Replication - physiology
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1006/cyto.2000.0798

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-α and viral replication was inhibited by neutralization of endogenous TNF-α. However, HIV-1 replication was strongly upregulated in minus clones by exogenous TNF-α, 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-α as one correlate that contributes to the higher ability of U937-plus clones to sustain HIV-1 replication. Furthermore, we suggest that TNF-α 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.