The phorbol ester TPA strongly inhibits HIV-1-induced syncytia formation but enhances virus production: possible involvement of protein kinase C pathway.
Cocultivation of MOLT-4 and MOLT-4/HIVHTLV-IIIB cells with more than 0.01 ng/ml of 12-O-tetradecanoylphorbol-13-acetate (TPA) for 20 hr strikingly inhibited HIV-induced syncytia formation resulting from cell to cell infection. Interestingly, the production of HIV-specific p24 antigen in the culture fluid was significantly enhanced by TPA. TPA down-modulated the expression of CD4. CD4 is essential for syncytia formation through interaction with viral envelope protein gp120 on the surface of MOLT-4 cells. The effects of TPA on syncytia formation and on CD4 expression were specifically interfered with by nontoxic doses of blockers of protein kinase C (PKC) such as staurosporine and H7. These data suggest that (1) TPA inhibits HIV-induced syncytia formation through down-modulation of CD4 molecules on the surface of MOLT-4 cells and (2) PKC may play an important role in cell to cell as well as in cell-free infection of HIV.
Chowdhury
I H
IH
Department of Virology and Parasitology, Yamaguchi University School of Medicine, Japan.
Koyanagi
Y
Y
Kobayashi
S
S
Hamamoto
Y
Y
Yoshiyama
H
H
Yoshida
T
T
Yamamoto
N
N
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D002460:Cell Line; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D015683:Gene Products, gag / Q000378:metabolism; D016655:HIV Core Protein p24; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D008213:Lymphocyte Activation / Q000187:drug effects; D008561:Membrane Fusion; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019311:Staurosporine; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014758:Viral Core Proteins / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects*
D000470:Alkaloids; D015683:Gene Products, gag; D016655:HIV Core Protein p24; D014758:Viral Core Proteins; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate