Influenza virus interactions

Animal V. The first stage of infection is adsorption of the vims to the exterior surface of the animal cell membrane. Adsorption occurs by interaction between a virus-coded protein on the surface of the virion and a receptor moleeule on the cell membrane. Most cell receptors are glycoproteins. Moreover, they are normal membrane glycoproteins with specific functions unrelated to virus infection. The interaction is specific. Thus, the binding protein of influenza virus interacts with the o2 3 linked terminal sialic add residue of the host cell membrane glycopFOtein treatment of a cell with sialidase (neuraminidase) renders it resistant to infection, and glycoproteins with al 6 linked siaUc acid do not serve as receptors. Under natural conditions, the presence of appropriate receptor molecules on the cell membrane is a precondition for virus infection, i.e. in the absence of receptors, the cell is not permissive for virus infection... 

Analysis of Potential Binding Interactions within the Influenza Virus Sialidase Active Site... 

Importantly, the crystal structure of 34 complexed with N9 sialidase (Fig. 8) indicated differences in the orientation of the guanidino group in subsite S2, and in its interaction with the active site residues, compared to that of zanamivir (Babu et al. 2000). These differences have implications for cross-reactivity of 34 with zanamivir-resistant influenza viruses that have Glul 19 mutations in the sialidase S2 subsite (see Sect. 5.1). 

Treatment via chelation has been observed for 2-acetylpyridine thiosemi-carbazone derivatives, which have been found to possess inhibitory activity for the RNA-polymerases of the influenza virus [133]. The iron(III) complexes were shown to be 3 to 6 times more active as inhibitors of partially purified ribonucleotide reductase (no added iron) compared to uncomplexed thiosemi-carbazone [128]. Raina and Srivastava [134] prepared and characterized low spin iron(III) complexes of 2-acetylpyridine thiosemicarbazone, [Fe(8-H)2A] (A = NO3, OH, Cl, N3, NCS or NO2), which were proposed as being seven-coordinate. However, all but the azide complex are 1 1 electrolytes in DMF and their solid ESR spectra are rhombic with the g-values being about 2.20,2.15 and 2.00. Of the six complexes, the azide ion seems to interact ihost strongly with the iron(III) center. 

It had been known since 1941 that red blood-cells are agglutinated by fluids containing influenza virus. In 1942, G. K. Hirst proved that purified influenza virus is quickly and quantitatively adsorbed on red cells, but that, after the elapse of several hours, the virus particle, apparently intact, has come off the surface of the red cells. After this treatment, cells were unable to be agglutinated by influenza virus or to adsorb virus particles. The problem of the interaction of influenza virus with red cells was attacked in a comprehensive manner by Sir Macfarlane Burnet and his coworkers in Melbourne in the period of... 

Chlordane interacts with other chemicals to produce additive or more-than-additive toxicity. For example, chlordane increased hepatotoxic effects of carbon tetrachloride in the rat (USEPA 1980 WHO 1984), and in combination with dimethylnitrosamine acts more than additively in producing liver neoplasms in mice (Williams and Numoto 1984). Chlordane in combination with either endrin, methoxychlor, or aldrin is additive or more-than-additive in toxicity to mice (Klaassen et al. 1986). Protein deficiency doubles the acute toxicity of chlordane to rats (WHO 1984). In contrast, chlordane exerts a protective effect against several organophosphorus and carbamate insecticides (WHO 1984), protects mouse embryos against influenza virus infection, and mouse newborns against oxazolone delayed hypersensitivity response (Barnett et al. 1985). More research seems warranted on interactions of chlordane with other agricultural chemicals. 

The initial step in the sequence of events leading to influenza virus infections in mammalian hosts is mediated by the multiple attachment of virus particles to host sialoside receptors in the nasopharynx [41]. These receptors consist largely of cell surface sialylated glycoproteins and gangliosides. The subsequent steps involve receptor-mediated endocytosis with ensuing release of the viral nucleo-plasmid. The first event responsible for the receptor-virus interaction is therefore an attractive target for both antiviral and related microbial intervention. 

---