Ampelopsin, a small molecule inhibitor of HIV-1 infection targeting HIV entry.
OBJECTIVE
To investigate the anti-HIV effects of ampelopsin and its interaction with HIV-1 coreceptor CXCR4.


METHODS
Through anti-virus experiments in vitro, the inhibitory effect of ampelopsin on HIV-1 infection was verified. Chemotaxis assay was performed to show the ability to induce PBMCs migration by ampelopsin, RANTES and SDF-1alpha. Fluorescence labelling monoclonal antibody was utilized to observe the interaction of ampelopsin and CXCR4. Mice immunosuppressant model was also established to detail the role ampelopsin played in regulating cellular immunological functions.


RESULTS
Ampelopsin could protect sensitive cells against HIV-1 infection and dramatically reduce HIV-1 antigen P24 expression. HIV-1SF33 attaching to MT-4 cells was interfered by ampelopsin, and the EC50 was 0.175 mg/mL for cellular protection and 0.024 mg/mL for P24 inhibition. At co-cultivating phase, EC50 was 0.229 mg/mL and 0.197 mg/mL respectively. Furthermore, the EC50 was 0.179 mg/mL and 0.348 mg/mL in acute infection. Human PBMCs migration was induced after being challenged with ampelopsin or chemokines, and synergistic action was observed during co-treatment. Ampelopsin alone resulted in maximal chemotaxis at 1 mg/mL. HIV-1 co-receptor CXCR4 on the surface of PBMCs was decreased by internalization, which indicated the effect of ampelopsin on CXCR4. About 70% CXCR4 was reduced by ampelopsin at 1 mg/mL. Ampelopsin also augmented cellular immunological functions in immunosuppressive mice.


CONCLUSIONS
Ampelopsin displays a strong inhibitive role during HIV-1 absorption, incubation and acute infection. These results are coincident with its immune enhancement.
Liu
De-Yu
DY
Department of Chemistry, Zhongshan Medical College, Sun Yat-sen University, Guangzhou 510089, Guangdong, China. liudy@gzsums.edu.cn
Ye
Jian-Tao
JT
Yang
Wen-Hui
WH
Yan
Jin
J
Zeng
Chang-Hong
CH
Zeng
Sa
S
D032421:Ampelopsis / Q000737:chemistry; D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology*; D002460:Cell Line; D018946:Chemokine CCL5 / Q000494:pharmacology; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte; D015536:Down-Regulation; D004365:Drugs, Chinese Herbal; D005419:Flavonoids / Q000191:economics / Q000302:isolation & purification / Q000494:pharmacology*; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000378:metabolism / Q000472:pathogenicity*; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D018517:Plant Roots / Q000737:chemistry; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000187:drug effects*; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D019380:Anti-HIV Agents; C515255:CXCL12 protein, human; D018946:Chemokine CCL5; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D004365:Drugs, Chinese Herbal; D005419:Flavonoids; D007376:Interleukin-2; D019718:Receptors, CXCR4; C106407:ampelopsin