Inhibition of HIV-2(ROD) replication in a lymphoblastoid cell line by the alpha1-antitrypsin Portland variant (alpha1-PDX) and the decRVKRcmk peptide: comparison with HIV-1(LAI).
We investigated the effects of alpha1-antitrypsine Portland variant (alpha1-PDX) and decanoylRVKRchloromethylketone (decRVKRcmk) on HIV-2(ROD) replication in the Jurkat lymphoblastoid cell line. To this end, cells were stably transfected with the alpha1-PDX (J-PDX) and used as targets for HIV-2(ROD) infection. Controls were prepared with the empty vector (J-pcDNA3). HIV-2(ROD) and HIV-1(LAI) replications were significantly inhibited and delayed in the presence of the alpha1-PDX protein. When decRVKRcmk was used at 35 microM, inhibition rates were 70-80% for HIV-2(ROD) and HIV-1(LAI), while total inhibition occurred at 70 microM. Control peptides consisting of decanoylRVKR and acetylYVADcmk had no effect. In the presence of the alpha1-PDX or the decRVKRcmk at 35 microM, the infectivity of HIV-2(ROD) and HIV-1(LAI) produced was 3-4-fold lower. Both molecules inhibited syncytium formation by HIV-2(ROD) and HIV-1(LAI) to a considerable extent. Finally, the inhibition of viral replication was correlated with the ability of the decRVKRcmk at 35 and 70 microM and of the alpha1-PDX, to inhibit the processing of envelope glycoprotein precursors. The alpha1-PDX protein and the decRVKRcmk peptide at 35 microM inhibited HIV-2 and HIV-1 to a similar level suggesting that identical or closely related endoproteases are involved in the maturation of their envelope glycoprotein precursors into surface and transmembrane glycoproteins. The significant inhibition observed with alpha1-PDX indicates that furin or furin-like endoproteases appear to play a major role in the maturation process.
Bahbouhi
B
B
Laboratoire dimmuno-virologie, Université Paul Sabatier, Bât 4R3, UFR/SVT, 118, route de Narbonne, 31062 cedex, Toulouse, France. bahraoui@cict.fr
Bendjennat
M
M
Chiva
C
C
Kogan
M
M
Albericio
F
F
Giralt
E
E
Seidah
N G
NG
Bahraoui
E
E
D000590:Amino Acid Chloromethyl Ketones; D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015686:Gene Products, env / Q000378:metabolism; D015726:Giant Cells / Q000187:drug effects / Q000821:virology; D019302:HIV Envelope Protein gp160 / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D015498:HIV-2 / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D011498:Protein Precursors / Q000378:metabolism; D019065:Virus Assembly / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects*; D000515:alpha 1-Antitrypsin / Q000494:pharmacology*; D054299:env Gene Products, Human Immunodeficiency Virus
D000590:Amino Acid Chloromethyl Ketones; D019380:Anti-HIV Agents; D015686:Gene Products, env; D019302:HIV Envelope Protein gp160; D010455:Peptides; D011498:Protein Precursors; D000515:alpha 1-Antitrypsin; C113421:alpha 1-antitrypsin Portland; C460143:decanoylRVKRchloromethylketone; D054299:env Gene Products, Human Immunodeficiency Virus; C066315:gp140 envelope protein, Human immunodeficiency virus 2