Abstract
Ribosome inactivating proteins (RIPs) inhibit protein synthesis by depurinating the large ribosomal RNA and some are found to possess anti-human immunodeficiency virus (HIV) activity. Maize ribosome inactivating protein (RIP) has an internal inactivation loop which is proteolytically removed for full catalytic activity. Here, we showed that the recombinant active maize RIP protected chimeric simian-human immunodeficiency virus (SHIV) 89.6-infected macaque peripheral blood mononuclear cells from lysis ex vivo and transiently reduced plasma viral load in SHIV89.6-infected rhesus macaque model. No evidence of immune dysregulation and other obvious side-effects was found in the treated macaques. Our work demonstrates the potential development of maize RIP as an anti-HIV agent without impeding systemic immune functions.
Highlights
Ribosome inactivating proteins (RIPs) are RNA N-glycosidases
The exclusive observation that the active form of maize RIP differentially enhanced the cell survival of infected peripheral blood mononuclear cells (PBMC), but not healthy PBMC, hints that the protective effect is attributed to the antiviral property of His-TAT-MOD
Apart from the potent cytotoxicity caused by rRNA depurination, RIPs are well-known for inhibition of viruses, with anti-human immunodeficiency virus (HIV) activity attracting the most attention
Summary
Ribosome inactivating proteins (RIPs) are RNA N-glycosidases. They cleave the N-glycosidic bond of adenine-4324 located at the GAGA hairpin of the sarcin/ricin loop of 28S rRNA and stop protein synthesis.RIPs are highly cytotoxic and they have been developed into immunotoxins, anti-viral and anti-tumor agents [1,2,3]. Ribosome inactivating proteins (RIPs) are RNA N-glycosidases. Type 1 RIPs, such as trichosanthin (TCS) and pokeweed antiviral protein (PAP), exist as a single polypeptide. TCS has been used in Chinese folk medicine for centuries to terminate gestation at early or mid-term stages and to treat hydatidiform moles [4] which may be explained by the high sensitivity of syncytiotrophoblasts towards the cytotoxic RIPs and undergo fragmentation [5]. It is well-known that type 1 RIPs possess anti-HIV properties. Saporin and luffin inhibited HIV-1 integrase and prevented insertion of viral DNA into the host’s chromosome [7]
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