TAILIEUCHUNG - Báo cáo y học: "GPG-NH2 acts via the metabolite aHGA to target HIV-1 Env to the ER-associated protein degradation pathway"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Retrovirology cung cấp cho các bạn kiến thức về ngành y đề tài: "GPG-NH2 acts via the metabolite aHGA to target HIV-1 Env to the ER-associated protein degradation pathway. | Jejcic et al. Retrovirology 2010 7 20 http content 7 1 20 RETR0VIR0L0GY RESEARCH Open Access GPG-NH2 acts via the metabolite aHGA to target HIV-1 Env to the ER-associated protein degradation pathway Alenka Jejcic1 Stefan Hoglund2 Anders Vahlne1 Abstract Background The synthetic peptide glycyl-prolyl-glycine amide GPG-NH2 was previously shown to abolish the ability of HIV-1 particles to fuse with the target cells by reducing the content of the viral envelope glycoprotein Env in progeny HIV-1 particles. The loss of Env was found to result from GPG-NH2 targeting the Env precursor protein gp160 to the ER-associated protein degradation ERAD pathway during its maturation. However the antiviral effect of GPG-NH2 has been shown to be mediated by its metabolite a-hydroxy-glycineamide aHGA which is produced in the presence of fetal bovine serum but not human serum. In accordance we wanted to investigate whether the targeting of gp160 to the ERAD pathway by GPG-NH2 was attributed to its metabolite aHGA. Results In the presence of fetal bovine serum GPG-NH2 its intermediary metabolite glycine amide G-NH2 and final metabolite aHGA all induced the degradation of gp160 through the ERAD pathway. However when fetal bovine serum was replaced with human serum only aHGA showed an effect on gp160 and this activity was further shown to be completely independent of serum. This indicated that GPG-NH2 acts as a pro-drug which was supported by the observation that it had to be added earlier to the cell cultures than aHGA to induce the degradation of gp160. Furthermore the substantial reduction of Env incorporation into HIV-1 particles that occurs during GPG-NH2 treatment was also achieved by treating HIV-1 infected cells with aHGA. Conclusions The previously observed specificity of GPG-NH2 towards gp160 in HIV-1 infected cells resulting in the production of Env gp120 gp41 deficient fusion incompetent HIV-1 particles was most probably due to the action of the GPG-NH2 .

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