guanosine-monophosphate and Virus-Diseases

Innate immunity is the first line of host defense against viral infection. After invading into the cells, pathogen-associated-molecular-patterns derived from viruses are recognized by pattern recognition receptors to activate the downstream signaling pathways to induce the production of type I interferons (IFN-I) and inflammatory cytokines, which play critical functions in the host antiviral innate immune responses. Guanylate-binding proteins (GBPs) are IFN-inducible antiviral effectors belonging to the guanosine triphosphatases family. In addition to exerting direct antiviral functions against certain viruses, a few GBPs also exhibit regulatory roles on the host antiviral innate immunity. However, our understanding of the underlying molecular mechanisms of GBPs' roles in viral infection and host antiviral innate immune signaling is still very limited. Therefore, here we present an updated overview of the functions of GBPs during viral infection and in antiviral innate immunity, and highlight discrepancies in reported findings and current challenges for future studies, which will advance our understanding of the functions of GBPs and provide a scientific and theoretical basis for the regulation of antiviral innate immunity.

Topics: Carrier Proteins; GTP-Binding Proteins; Guanosine Monophosphate; Host-Pathogen Interactions; Humans; Immunity, Innate; Signal Transduction; Virus Diseases

The effect of certain antiviral compounds said to act because of an increased permeability of virally infected cells has been tested in SFV-infected BHK cells. The time at which SFV-infected BHK cells become sensitive to the action of GppCH2p is more than an hour later than the time at which protein synthesis in such cells becomes depressed. The uptake of [3H]GppCH2p is the same in infected and uninfected cells, whether measured at 19 or 37 degrees C. We conclude that GppCH2p, and probably other 'impermeant' inhibitors of protein synthesis also, affect virally-infected cells selectively not because of an increased permeability, but because of a general impairment of protein synthesis in such cells.

Topics: Animals; Antiviral Agents; Cell Line; Cell Membrane Permeability; Cricetinae; Diphosphonates; Guanine Nucleotides; Guanosine Monophosphate; Guanosine Triphosphate; Kidney; Protein Biosynthesis; Semliki forest virus; Togaviridae Infections; Virus Diseases

3-Deazaguanine (ICN 4221), 3-deazaguanosine (ICN 4793), and 3-deazaguanylic acid (ICN 5412) represent a new class of synthetic guanine analogs having antiviral activity. In vitro, nine ribonucleic acid and seven deoxyribonucleic acid viruses were inhibited, including influenza, parainfluenza, rhino-, vesicular stomatitis, adeno-, herpes-, cytomegalo-, vaccinia, pseudorabies, and myxoma viruses. They were effective orally against influenza types A and B and parainfluenza type 1 (Sendai) virus infections in mice, with a therapeutic index of 16 against the latter two viruses. The course of herpes encephalitis was altered only when the drugs were applied directly into the brain. In addition, these drugs were effective inhibitors of Friend leukemia virus-induced splenomegaly in mice; treatment also produced extensions of life in these animals.

Topics: Animals; Antiviral Agents; Cells, Cultured; Chick Embryo; Cytopathogenic Effect, Viral; Guanine; Guanine Nucleotides; Guanosine; Guanosine Monophosphate; Humans; In Vitro Techniques; Male; Mice; Rabbits; Virus Diseases; Virus Replication