Herpes virus proteins

Since the pioneering work of Kleymann et al. (2002), Betz et al. (2002), Baumeister et al. (2007), and Crute et al. (2002), who showed that compounds identified as inhibitors of the helicase-primase enzyme complex could alleviate herpesvirus-induced disease in animal models, the attention of researchers developing antiviral compounds has been drawn more and more towards the virus-encoded helicases, particularly those of Herpes viruses and of RNA viruses such as Hepatitis C Virus (HCV) and SAKS coronavirus (SARS-CoV). Enzyme activity is usually assayed by measuring NTPase activity in the presence of an appropriate nucleic acid co-substrate although, more recently, novel fiuorimetric and luminescence principles have been applied to the measurement of strand unwinding and/or translocation of the protein along the nucleic acid (Frick 2003, 2006). 

CP coat protein CtxB cholera toxin B subunit scFv single chain Fv antibody fragment TMOF trypsin modulating oostatic factor MAB monoclonal antibody GFP green fluorescent protein CPV Canine parvovirus BHV Bovine herpes virus FMDV Foot and mouth disease virus HCV Hepatitis C virus HRV Human rhino Virus MEV Mink enteritis virus MHV Murine hepatitis virus MV Measles virus RSV Respiratory syncytial virus... 

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). 

Antibodies against the virus but also amantadine and derivatives, interfere with host cell penetration. There are nucleoside analogues such as aciclovir and ganciclovir, which interfere with DNA synthesis, especially of herpes viruses. Others like zidovudine and didanosine, inhibit reverse transcriptase of retroviruses. Recently a number of non-nucleoside reverse transcriptase inhibitors was developed for the treatment of HIV infections. Foscarnet, a pyrophosphate analogue, inhibits both reverse transcriptase and DNA synthesis. Protease inhibitors, also developed for the treatment of HIV infections, are active during the fifth step of virus replication. They prevent viral replication by inhibiting the activity of HIV-1 protease, an enzyme used by the viruses to cleave nascent proteins for final assembly of new vi-rons. 

Perez-Filgueira, D.M., Zamorano, PL, Dominguez, M.G., Taboga, O., Del Medico Zajac, M.P., Puntel, M., Romera, S.A., Morris, T.J., Borca, M.V., Sadir, A.M. (2003). Bovine herpes virus gD protein produced in plants nsing a recombinant tobacco mosaic virus (TMV) vector possesses authentic antigenicity. Vaccine 21 4201 209. 

Gretch, D R., Suter, M, and Stinski, M. F (1987) The use of biotinylated monoclonal antibodies and streptavidin affinity chomatography to isolate Herpes virus hydrophobic proteins or glycoproteins Anal Biochem 163, 270-277... 

The ongoing clinical trials include the use of adenovirus and herpes virus vectors. One example of adenoviral vector is ONYX-015, which lacks E1B protein, required for replication with a normal p53 pathway and RNA export during viral replication. It has been used to treat squamous cell carcinoma of the head and neck and has also been tested as a preventive treatment for oral precancerous tissue. The concept behind using this vector is that ONYX-015 will proliferate in p53 pathway-deficient tumor cells and kill them. 

Honess RW, Roizman B (1974) Regulation of herpes virus macro-malecular synthesis Cascade regulation of three groups of viral proteins. J Virol 14 8-19. 

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