Ribosome inactivating proteins (RIPs) are a group of plant enzymes that inhibit polypeptide chain elongation by inactivating the ribosome . All plant RIPs share the common property of inactivating ribosomes and inhibiting protein synthesis. RIPs damage ribosomes in an irreversible manner by removing adenine residue from 28S rRNA by N-glycosidase activity (Fig. 1). The removal of one adenine base renders the 60S subunit of eukaryotic ribosomes unable to bind the elongation factor 2 (EF-2), with consequent arrest of protein synthesis . RIPs are classified into three types: type Ⅰ composed of a single polypeptide chain; type Ⅱ, a heterodimer consisting of an A-chain, functionally equivalent to a type Ⅰ, which is attached to a sugar-binding B chain; Type Ⅲ, a single chain containing an extended carboxyl-terminal domain with unknown function [20, 25].
Figure 1. Mechanism of action of RIPs: A specific N-glycosidase activity cleaves adenine (A4324) which is located in sarcin/ricin loop of the ribosomal RNA of the large subunit. The reaction product of the RNA N-glycosidase (Deadenylated rRNA) acts as a substrate for 'ribosomal RNA apurinic site specific lyase' (RALyase), which cleaves the phosphodiester bond 3' end. The reaction products are a short (4325-4785) 3'-end fragment and a long (1-4324) 5'-fragment with free 3'-hydroxyl terminus .
Ribosome inactivating proteins (RIPs) exhibit important antiviral properties against viruses by virtue of their broad-spectrum antiviral activity. RIPs inhibit replication of RNA as well as DNA viruses. Antiviral research has been focused on RIPs that interfere with various parts of the viral life cycle and most of the recent work has been focused on the ability of RIPs to act against Human immunodeficiency virus (HIV) [11, 21]. Trichosanthin (Trichosanthes kirilowii), PAP (Poke weed americana) and MAP30 (Momordica charantia) have been reported to inhibit HIV-1 replication in vitro . Trichosanthes was the first RIP to be tested in phase I clinical trials during a time when AZT (zidovudine) was the only drug approved to treat HIV infection . However, the exact mechanism of antiviral activity is still not clear. It was initially thought it involved inactivation of the host cell ribosomes, leading to inhibition of viral protein translation and host cell death. However, with the help of recombinant techniques, mutated RIPs were produced and it was possible to ascertain that the ribosome-inactivating and antiviral activities could be separated . The aim of this review is to describe several plant RIPs and discuss recent progress in establishing the anti-viral activities of these proteins.
RIPs have antiviral activity against plant, fungal and animal viruses. The antiviral activity against animal virus has led to numerous studies on the effect of RIPs. Investigations on RIP were started with the hope that these could be used for AIDS therapy [12, 13]. Important advances were made in the field of RIPs from plant, thereby focusing on their in vitro anti-HIV model as well as on their mechanism of action. The replication of HIV was observed to be inhibited by several RIPs, including MAP30, GAP31, PAP and trichosanthin .
Ribosome Inactivating Proteins from Plants Inhibiting Viruses *
- Received Date: 22 September 2011
- Accepted Date: 26 October 2011
Abstract: Many plants contain ribosome inactivating proteins (RIPs) with N-glycosidase activity, which depurinate large ribosomal RNA and arrest protein synthesis. RIPs so far tested inhibit replication of mRNA as well as DNA viruses and these proteins, isolated from plants, are found to be effective against a broad range of viruses such as human immunodeficiency virus (HIV), hepatitis B virus (HBV) and herpes simplex virus (HSV). Most of the research work related to RIPs has been focused on antiviral activity against HIV; however, the exact mechanism of antiviral activity is still not clear. The mechanism of antiviral activity was thought to follow inactivation of the host cell ribosome, leading to inhibition of viral protein translation and host cell death. Enzymatic activity of RIPs is not limited to depurination of the large rRNA, in addition they can depurinate viral DNA as well as RNA. Recently, Phase I/II clinical trials have demonstrated the potential use of RIPs for treating patients with HIV disease. The aim of this review is to focus on various RIPs from plants associated with anti-HIV activity.