Opposite effects of SDF-1 on human immunodeficiency virus type 1 replication.
The alpha-chemokine SDF-1 binds CXCR4, a coreceptor for human immunodeficiency virus type 1 (HIV-1), and inhibits viral entry mediated by this receptor. Since chemokines are potent chemoattractants and activators of leukocytes, we examined whether the stimulation of HIV target cells by SDF-1 affects the replication of virus with different tropisms. We observed that SDF-1 inhibited the entry of X4 strains and increased the infectivity of particles bearing either a CCR5-tropic HIV-1 envelope or a vesicular stomatitis virus G envelope. In contrast to the inhibitory effect of SDF-1 on X4 strains, which is at the level of entry, the stimulatory effect does not involve envelope-receptor interactions or proviral DNA synthesis. Rather, we observed an increased ability of Tat to transactivate the HIV-1 long terminal repeat in the presence of the chemokine. Therefore, the effects of SDF-1 on the HIV-1 life cycle can be multiple and opposite, including both an inhibition of viral entry and a stimulation of proviral gene expression.
Maréchal
V
V
Laboratoire Rétrovirus et Transfert Génétique, URA CNRS 1157, 75724 Paris Cedex 15, France.
Arenzana-Seisdedos
F
F
Heard
J M
JM
Schwartz
O
O
D019380:Anti-HIV Agents / Q000494:pharmacology*; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology*; D015696:Gene Products, tat / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D008214:Lymphocytes / Q000821:virology; D009000:Monocytes / Q000821:virology; D014158:Transcription, Genetic; D014779:Virus Replication; D054322:tat Gene Products, Human Immunodeficiency Virus
D019380:Anti-HIV Agents; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D015696:Gene Products, tat; D054322:tat Gene Products, Human Immunodeficiency Virus