Interferon virus

Interferons [alFN, piFN and ylFN]. Interferons are a family of glycosylated proteins and are cytokines which are produced a few hours after cells have been infected with a virus. Interferons protect cells from viral infections and have antiviral activities at very low concentrations ( 3 x 10 M, less than 50 molecules are apparently sufficient to protect a single cell). Double stranded RNA are very efficient inducers of IFNs. There are three main types of IFNs. The aIFNs are synthesised in lymphocytes and the piFNs are formed in infected fibroblasts. The a and P families are fairly similar consisting of ca 166 to 169 amino acids. Although ylFNs are also small glycosylated proteins (ca 146 amino acids), they are different because they are not synthesised after viral infections but are produced by lymphocytes when stimulated by mitogens (agents that induced cell division). 

Antibodies are proteins made in the body in response to foreign substances such as bacteria or viruses. Interferon is an important antibody because it offers general protection against viruses (many antibodies target specific invaders). 

Human Cytomegalovirus Hepatitis C Virus Hepatitis Delta Virus Human Herpes Virus-6 Human Immunodeficiency Virus Herpes Simplex Virus Interferons... 

In spite of the efficacy of exogenous interferon, the major search has been for Interferon inducers. Synthetic polymers have been effective inducers and some of the characteristics apparently necessary for activity are as follows a large molecule with a high density of free anionic groups, not readily degradable and not readily eliminated. Agents with these characteristics include polymers of maleic anhydrides, polyacrylates and carboxylates. Polyacrylic acid (PAA) and polymethacrylic acid (PMAA) have induced Interferon in tissue culture and protected mice infected with Mengo virus and vaccinia and vesicular stomatitis viruses,76. Salts of polyvinyl sulfate appear to have dual activity since they induce interferon activity in mice but not in tissue culture, and the antiviral activity exerted is not correlated with virus interferon sensitivity. ... 

Each bottle for interferon production received thearborvirus preparation in medium 199 (0.5 ml) and further medium 199 (50 ml) some bottles received only medium 199 (50 ml) and no virus and served as controls. The bottles were incubated for 3 to 5 days at 36°C. 

At this stage the interferon preparations were assayed and submitted to safety tests for the absence of contaminating viruses. 

Rhesus monkey kidney infected with Semliki Forest arborvirus gave interferon of tltre 1.5 log interferon units/2 ml. (The interferon unit, determined in a volume of 2 ml, is the dilution of interferon which produced a half-maximal score for degree of cytopathic effect In virus-infected tissue culture tubes at the time when the control without interferon first showed the maximal score.)... 

Each interferon preparation was ultracentrifuged at 20,000 revolutions per minute for one hour to remove tissue debris and inactivated virus. The supernatant was dialyzed against distilled water (1 400) for 24 hours at4°C. The material was then freeze-dried. The dried product was reconstituted in one-tenth of the original volume in distilled water and dispensed into ampoules. Reconstituted solutions were assayed for interferon activity, examined for toxicity, and tested for sterility. 

For the pathogenesis of multiple sklerosis, autoimmune T-lymphocy tes play a predominant role, which are directed against components of the neural myelin sheath. T-lymphocy tes by secreting cytokines such as interferon y maintain the chronic inflammation which destructs the myelin sheath. Also cytotoxic T-lymphocytes may participate directly. The cause of multiple sklerosis is unknown. Significantly increased antibody titers against several vitusses, mostly the measles virus, point to a (latent) virus infection initiating the disease. 

Double stranded (ds) RNA is not a constituent of a normal cells but is produced during replication of many RNA and DNA viruses either as an obligatory intermediate or as a side product. As a foreign molecule, double stranded RNA induce the secretion of interferon (EFN) from lymphocytes, neutrophils and fibroblasts. 

Interferons (EFNs) are a family of multifunctional secreted proteins in vertebrates. Their most prominent functions are their antiviral properties on homologous cells against a wide range of viruses. It is important to note that prior exposure to EFN is required to render cells resistant to viral infection and replication. In contrast to antibodies, EFNs have no direct neutralizing effect on viruses. 

A major limitation in the development of anti-HCV compounds was the lack of a virus replication system. This was finally overcome with the development of a novel replicon system that directed persistent replication in a cell culture format (Lohmann et al. 1999). Using such a system, it was possible to demonstrate antiviral activity of an NS3/4A inhibitor in a cell culture assay, and demonstrate potency on par with treatment with interferon-a (Pause et al. 2003). 

Abstract In 2007, the world celebrated the 50th anniversary of the discovery of interferon (IFN) by Isaacs and Lindemnann. Subsequently, the IFN-a gene was cloned, fully sequenced and IFN-a was produced in recombinant form. Recombinant IFN-a is now used as the basis for treatment of chronic hepatitis C virus infection and can also be used to treat certain forms of chronic hepatitis B virus infections. IFNs have also been used in other viral infections, although with less success. The antiviral mechanisms of IFNs are reviewed in this chapter as well as the utility of IFNs in the treatment of persistent viral infections. 

Ank N, West H, Bartholdy C, Eriksson K, Thomsen AR, Paludan SR (2006) Lambda interferon (IFN-lambda), a type III lEN, is induced by viruses and IFNs and displays potent antiviral activity against select virus infections in vivo. J Virol 80 4501 509... 

De Rosa EG, Bargiacchi O, Audagnotto S, Garazzino S, Cariti G, Veronese L, Raiteri R, CaUeri G, Di Perri G (2006) The early HCV RNA dynamics in patients with acute hepatitis C treated with pegylated interferon-alpha2b. Antivir Ther 11 165-171 Di Bisceglie A (1997) Hepatitis D virus. Marcel Dekker, NY... 

Enomoto M, Tamori A, Kohmoto MT, Hayashi T, Jomura H, Habu D, Sakaguchi H, Takeda T, Kawada N, Seki S, Shiomi S, Koh N, Nishiguchi S (2007) Lamivudine and IFN-beta sequential therapy in HBe antigen-positive patients with chronic hepatitis B virus genotype C infection. J Interferon Cytokine Res 27 201-207... 

Fernie BF, Poli G, Fauci AS (1991) Alpha interferon suppresses virion but not soluble human immunodeficiency virus antigen production in chronically infected T-lymphocytic cells. J Virol 65 3968-3971... 

Frese M, Schwarzle V, Barth K, Krieger N, Lohmann V, Mihm S, Haller O, Bartenschlager R (2002) Interferon-gamma inhibits replication of subgenomic and genomic hepatitis C virus RNAs. Hepatology 35 694-703... 

Hong SH, Cho O, Kim K, Shin HJ, Kotenko SV, Park S (2007) Effect of interferon-lambda on replication of hepatitis B virus in human hepatoma cells. Virus Res 126 245-249 Hoofnagle JH, Mullen KD, Jones DB, Rustgi V, Di BiscegUe A, Peters M, Waggoner JG, Park Y, Jones EA (1986) Treatment of chronic non-A, non-B hepatitis with recombinant human alpha interferon. A preliminary report. N Engl J Med 315 1575-1578 Horiike N, Onji M (2003) Combination therapy with interferon-alpha and ribavirin as im-munomodulators in patients with chronic hepatitis C. J Gastroenterol 38 302-304... 

Keeffe EB, Dieterich DT, Han SH, Jacobson IM, Martin P, Schiff ER, Tobias H, Wright TL (2006) A treatment algorithm for the management of chronic hepatitis B virus infection in the United States an update. Clin Gastroenterol Hepatol 4 936-962 Kim KI, Sasase N, Taniguchi M, Mita K, Kinoshita K, Togitani T, Shikata M, Kimura N, Izawa S, Ohtani A, Nakao K, Muramoto Y, Kim SR, Nabeshima S, Ishii F, Tanaka K, Hayashi Y (2005) Interferon-beta induction/interferon-alpha2b plus ribavirin therapy in patients with chronic hepatitis C. Int J Clin Pharmacol Res 25 71-76... 

Lampertico P, Del Ninno E, Manzin A, Donato MF, Rumi MG, Lunghi G, Morabito A, Clementi M, Colombo M (1997) A randomized, controlled trial of a 24-month course of interferon alfa 2b in patients with chronic hepatitis B who had hepatitis B virus DNA without hepatitis B e antigen in serum. Hepatology 26 1621-1625... 

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