Antiviral protein

Fig. 5.1 Regulators of pre- and post-integration latency. Pre-integration latency is regulated as the viral RNA is reverse transcribed into the proviral DNA (A). This is controlled by the avaUabdity of the nucleotide pool, half life of the forming proviral cDNA copy, and the interaction of the viral protein Vif with the cellular antiviral protein APOBEC, espedaUy family members 3G and 3R It is also regulated at the step of transport across the nuclear membrane through the availability of ATP as the process requires energy (B). Post-integration, the proviral DNA copy of the viral genome, is regulated maiiily by the avadabdity of host transcription factors, especially NF-kB and NFAT (C)...

Irvin, J.D. (1983) Pokeweed antiviral protein. Pharmacol. Ther. 21, 371-387. 

Lambert, J.M., Senter, P.D., Yau-Young, A., Blattler, W.A., and Goldmacher, V.S. (1985) Purified immuno-toxins that are reactive with human lymphoid cells Monoclonal antibodies conjugated to the ribosomeinactivating proteins gelonin and the pokeweed antiviral proteins./. Biol. Chem. 260, 12035-12041. 

Interferons (IFN) are glycoproteins that, among other products, are released from virus-infected cells. In neighboring cells, interferon stimulates the production of "antiviral proteins." These inhibit the synthesis of viral proteins by (preferential) destruction of viral DNA or by suppressing its translation. Interferons are not directed against a specific virus, but have a broad spectrum of antiviral action that is, however, species-specific. Thus, interferon for use in humans must be obtained from cells of human origin, such as leukocytes (IFN-a), fibroblasts (IFN-P), or lymphocytes (IFN-y). Interferons are also used to treat certain malignancies and autoimmune disorders (e.g., IFN-a for chronic hepatitis C and hairy cell leukemia IFN-p for severe herpes virus infections and multiple sclerosis). 

Interferon. Any of a family of glycoproteins that exert virus-nonspecific but host-specific antiviral activity by inducing the transcription of cellular genes coding for antiviral proteins that selectively inhibit the synthesis of viral RNA and proteins. Interferons have immunoregulatory functions and can inhibit the growth of nonviral intracellular parasites. 

Interferons induce synthesis of new antiviral proteins in non-infected cell. 

Other Bacterial vaccines and toxoids 1 Viral vaccines J Rickettsial vaccines Antisera Antiviral protein (interferon) Prophylaxis Therapy Chemotherapy Subunit vaccines sometimes available... 

Fig. 3.3 shows the principle behind the design of immunotoxins. A number of protein toxins of bacterial and plant origin are useful for the production of immunotoxins. These include the diphtheria toxin and pseudomonas exotoxin from bacteria, and ricin, arbin, pokeweed antiviral proteins, saporin, and gelonin from plants (Pastan et al, 1986 Pastan and FitzGerald, 1991). All of these toxins kill cells by entering the cells, and enzymatically inactivating the translational machinery of the cells. Some, such as diphtheria toxin, arbin, and ricin, are composed of two protein chains, A and B. The B chains bind to the cell-surface... 

Interferons were first characterized as antiviral proteins produced by host cells. Later it was found that interferons had antiproliferative activity and also served as modulating agents for macrophages and natural killer cells. 

Interferon. One of a family of proteins that are liberated by special host cells in the mammal in response to viral infection. The interferons attach to an infected cell, where they stimulate antiviral protein s)mthesis. 

On binding to the appropriate cellular receptor, the IFNs induce the synthesis of a cascade of antiviral proteins that... 

Interferons are generally stimulatory proteins that exert their activity through interactions with cell surface receptors, inducing cellular processes and enhancing specific gene translation (79). Interferons also regulate the expression of unique antiviral proteins such as MX protein, which alters microtubule formation and mitosis, and 2 -5 -oligoadenylate synthetase (2,5-0AS), which induces the destruction of viral RNA. 

Plant RlPs have been classified into three general types based on structure. Type 1 RlPs are monomeric V-glycosidase enzymes of approximately 30 kDa molecular weight and a basic isoelectric point they share a common secondary stmcture around the rRNA-binding cleft, as well as several specific active-site residues (Barbieri et al., 1993). Type 1 RlPs are frequently found in higher plants, but also have been isolated from at least one mushroom (Yao et al., 1998). The best-studied type 1 RlPs are pokeweed antiviral protein, saporin, and barley translation inhibitor (Nielsen and Boston, 2001). Type 1 RlPs are generally considered nontoxic because they lack an effective cell-binding or internalization apparatus. 

The ribosome conformations required for optimal RTA binding and catalysis are stiU under study (Endo et al., 1991 Macbeth and Wool, 1999 Chan et al., 2004 Mansouri et al., 2006). In addition to the rRNA, RTA may interact with specific protein components of the ribosome. Rat ribosomal proteins L9 and PO, both located in the acidic stalk of the ribosome, can be chemically cross-linked with RTA (Vater et al., 1995). Likewise, yeast ribosomal protein L3 interacts with pokeweed antiviral protein, and the binding is dependent on the presence of two specific amino acid residues that are highly conserved among eukaryotes (Hudak et al., 1999). 

Hudak, K.A., Dinman, J.D. and Turner, N.E. (1999) Pokeweed antiviral protein accesses ribosomes by binding to L3. J Biol Chem, 274, 3859-3864. 

Mansouri, S., NouroUahzadeh, E. and Hudak, K.A. (2006) Pokeweed antiviral protein depurinates the sarcin/ricin loop of the rRNA prior to binding of aminoacyl-tRNA to the ribosomal A-site. RNA, 12, 1683-1692. 

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