TY - JOUR
T1 - Induction of heat-shock protein 70 by prostaglandin A1 inhibits HIV-1 Vif-mediated degradation of APOBEC3G
AU - Sugiyama, Ryuichi
AU - Abe, Makoto
AU - Nishitsuji, Hironori
AU - Murakami, Yuko
AU - Takeuchi, Hiroaki
AU - Takaku, Hiroshi
N1 - Funding Information:
We thank Dr. Darlene Chen for providing pcDNA-A3G-HA and Haruki Naganuma and Hiroshi Koseki for their technical assistance. This work was supported in part by the following: a Grant-in-Aid for Science Research (C) from the Japan Society for the Promotion of Science (JSPS), Japan; a Grant-in-Aid for AIDS research from the Ministry of Health, Labor, and Welfare, Japan; and a Grant from the Strategic Research Foundation Grant-aided Project for Private Universities from the Ministry of Education, Culture, Sport, Science, and Technology, Japan (MEXT).
PY - 2013/9
Y1 - 2013/9
N2 - Previous studies have demonstrated that cyclopentenone prostaglandins (cyPGs) inhibit human immunodeficiency virus type 1 (HIV-1) replication in various cell types. This antiviral activity has been associated with the induction of heat-shock protein 70 (HSP70) in infected cells. We investigated a new role of prostaglandin A1 (PGA1) in the replication of HIV-1 in non-permissive cells. Because overexpression of HSP70 blocks the viral infectivity factor (Vif)-mediated degradation of APOBEC3G (A3G) via the ubiquitin-proteasome pathway, we examined the effects of PGA1 on A3G and HIV-1 replication. The induction of HSP70 synthesis by PGA1 blocked Vif-mediated A3G degradation and enhanced the incorporation of A3G into both wild-type and Vif-deficient viruses. Furthermore, we determined the viral titer of HIV-1 particles produced from PGA1-treated 293T cells. The induction of HSP70 synthesis by PGA1 significantly reduced the viral titer in the presence of A3G. Additionally, the p24 Gag antigen levels were dramatically reduced in non-permissive cells treated once or repeatedly with PGA1. Thus, we showed that PGA1 inhibits HIV-1 replication, at least in part, by blocking Vif-mediated A3G degradation.
AB - Previous studies have demonstrated that cyclopentenone prostaglandins (cyPGs) inhibit human immunodeficiency virus type 1 (HIV-1) replication in various cell types. This antiviral activity has been associated with the induction of heat-shock protein 70 (HSP70) in infected cells. We investigated a new role of prostaglandin A1 (PGA1) in the replication of HIV-1 in non-permissive cells. Because overexpression of HSP70 blocks the viral infectivity factor (Vif)-mediated degradation of APOBEC3G (A3G) via the ubiquitin-proteasome pathway, we examined the effects of PGA1 on A3G and HIV-1 replication. The induction of HSP70 synthesis by PGA1 blocked Vif-mediated A3G degradation and enhanced the incorporation of A3G into both wild-type and Vif-deficient viruses. Furthermore, we determined the viral titer of HIV-1 particles produced from PGA1-treated 293T cells. The induction of HSP70 synthesis by PGA1 significantly reduced the viral titer in the presence of A3G. Additionally, the p24 Gag antigen levels were dramatically reduced in non-permissive cells treated once or repeatedly with PGA1. Thus, we showed that PGA1 inhibits HIV-1 replication, at least in part, by blocking Vif-mediated A3G degradation.
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U2 - 10.1016/j.antiviral.2013.06.017
DO - 10.1016/j.antiviral.2013.06.017
M3 - Article
C2 - 23831493
AN - SCOPUS:84884577867
VL - 99
SP - 307
EP - 311
JO - Antiviral Research
JF - Antiviral Research
SN - 0166-3542
IS - 3
ER -