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Protein Pept Lett ; 26(12): 930-939, 2019.
Article in English | MEDLINE | ID: mdl-31441722

ABSTRACT

BACKGROUND: Supercharged GFP proteins were known as effective carriers for delivery of macromolecules into eukaryotic cells as well as fluorescent fusion tags for in vitro and in vivo detection. OBJECTIVE: Herein, anti-viral effects of +36 GFP and its anti-tumor effects were studied in vitro and in vivo, respectively. METHODS: We evaluated anti-HIV, anti-HSV, and anti-HCV effects of +36 GFP in vitro using ELISA, and real time PCR as common techniques for their detection, respectively. Moreover, we assessed the role of +36 GFP for eliciting HPV-related anti-tumor effects in mice due to the lack of HPV replication in vitro. RESULTS: Our data showed that +36 GFP efficiently enter the cells and augment the transfection rate of HPV16E7 antigen, as well. Furthermore, +36 GFP significantly reduced HCV, HIV and HSV replication up to 75%, 49% and 43% in HCV-infected Huh7.5 cells, HIV-infected Hela cells and HSV-infected Vero cells, respectively. On the other hand, mice immunization with +36 GFP complexed with HPV16 E7 antigen (+36GFP + E7) or fused to HPV16 E7 antigen (+36GFP-E7) elicited a higher Th1 cellular immune response with the predominant IgG2a, IgG2b, IFN-γ and Granzyme B levels than those induced by other groups. These regimens protected mice against TC- 1 tumor challenge (~ 67%) compared to E7 protein alone (~ 33%). These data suggested that +36 GFP can act as an anti-viral agent at certain dose due to its high efficiency in cell penetration in vitro and in vivo. CONCLUSION: Generally, +36 GFP targets viral replication in vitro as well as helps to suppress the growth of HPV-related tumors in vivo.


Subject(s)
Antiviral Agents/pharmacology , Green Fluorescent Proteins/genetics , Mutant Proteins/genetics , Papillomavirus Vaccines/genetics , Recombinant Fusion Proteins/genetics , Animals , Antineoplastic Agents/immunology , Antineoplastic Agents/pharmacology , Cell Line , Chlorocebus aethiops , Female , Granzymes/metabolism , Green Fluorescent Proteins/immunology , HIV/drug effects , HIV Infections/immunology , HIV Infections/prevention & control , Hepacivirus/drug effects , Human papillomavirus 16/drug effects , Humans , Immunity, Cellular , Interferon-gamma/metabolism , Mice, Inbred C57BL , Mutant Proteins/immunology , Mutant Proteins/pharmacology , Papillomavirus E7 Proteins/genetics , Papillomavirus E7 Proteins/immunology , Papillomavirus Vaccines/immunology , Recombinant Fusion Proteins/immunology , Recombinant Fusion Proteins/pharmacology , Virus Replication/drug effects
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