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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, RESULTS. Meshes: APOBEC-3G Deaminase, CD4-Positive T-Lymphocytes, Cell Line, Cytidine Deaminase, Gene Products, vif, HIV Infections, HIV-1, HeLa Cells, Humans, Leukocytes, Mononuclear, Mutation, Plasmids, Recombinant Fusion Proteins, Transcription, Genetic, vpr Gene Products, Human Immunodeficiency Virus.
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Is vpr14-88-Apobec3G fusion protein efficiently incorporated into Vif-positive HIV-1 particles and inhibits viral infection? Context: APOBEC3G (A3G), a deoxycytidine deaminase, is a potent host antiviral factor that can restrict HIV-1 infection. During Vif-negative HIV-1 replication, A3G is incorporated into HIV-1 particles, induces mutations in reverse transcribed viral DNA and inhibits reverse transcription. However, HIV-1 Vif counteracts A3G's activities by inducing its degradation and by blocking its incorporation into HIV-1 particles. Thus, it is interesting to elucidate a mechanism that would allow A3G to escape the effects of Vif in order to rescue its potent antiviral activity and to provide a possible novel therapeutic strategy for treating HIV-1 infection. In this study, we generated an R88-A3G fusion protein by fusing A3G to a virion-targeting polypeptide (R14-88) derived from HIV-1 Vpr protein and compared its antiviral effects relative to those of HA-tagged native A3G (HA-A3G). Our study showed that transient expression of the R88-A3G fusion protein in both Vif(-) and Vif(+) HIV-1 producing cells drastically inhibited viral infection in HeLa-CD4-CCR5-cells, CD4(+) C8166 T cells and human primary PBMCs. Moreover, we established CD4(+) C8166 T cell lines that stably express either R88-A3G or HA-A3G by transduction with VSV-G-pseudotyped lentiviral vector that harbor expression cassettes for R88-A3G or HA-A3G, respectively, and tested their susceptibility to Vif(+) HIV-1 infection. Our results clearly reveal that expression of R88-A3G in transduced CD4(+) C8166 cells significantly blocked Vif(+) HIV-1 infection. In an attempt to understand the mechanism underlying the antiviral activity of R88-A3G, we demonstrated that R88-A3G was efficiently incorporated into viral particles in the presence of Vif. Moreover, PCR analysis revealed that R88-A3G significantly inhibited viral cDNA synthesis during the early stage of Vif(+) virus infection.
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Our results clearly indicate that R88 delivers A3G into Vif(+) HIV-1 particles and inhibits infectivity and spread of the virions among CD4(+) T cells. This study provides evidence for an effective strategy to modify a host protein with innate anti-HIV-1 activity and rescue its potent anti-HIV potential in the presence of Vif. Further characterization and optimization of this system may lead to the development of an effective therapeutic approach against HIV-1 infection. Final Decision: yes