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.
Biswas
P
P
Laboaratory of Clinical Immunology, Scientific Institute H San Raffaele, Milan, Italy. Priscilla.Biswas@hsr.it
Mantelli
B
B
Delfanti
F
F
Cota
M
M
Vallanti
G
G
de Filippi C
Mengozzi
M
M
Vicenzi
E
E
Lazzarin
A
A
Poli
G
G
D001483:Base Sequence; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D020298:U937 Cells; D015854:Up-Regulation / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects / Q000502:physiology*
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D017931:DNA Primers; D016328:NF-kappa B; D012333:RNA, Messenger; D019718:Receptors, CXCR4; D014409:Tumor Necrosis Factor-alpha