Viruses influenza virus

Streptococcus pneumoniae Hepatitis B virus Influenza virus Hepatitis A virus... 

Subunit vaccines Immunogenic proteins or peptide antigens customized to specific antigenic determinants are purified from tissue culture HIV, rabies virus, influenza virus, hepatitis B virus... 

There is a wide variety of vectors used to deliver DNA or oligonucleotides into mammalian cells, either in vitro or in vivo. The most common vector systems are based on viral [retroviruses (9, 10), adeno-associated virus (AAV) (11), adenovirus (12, 13), herpes simplex virus (HSV) (14)] andnonviral [cationic liposomes (15,16), polymers and receptor-mediated polylysine-DNA] complexes (17). Other viral vectors that are currently under development are based on lentiviruses (18), human cytomegalovirus (CMV) (19), Epstein-Barr virus (EBV) (20), poxviruses (21), negative-strand RNA viruses (influenza virus), alphaviruses and herpesvirus saimiri (22). Also a hybrid adenoviral/retroviral vector has successfully been used for in vivo gene transduction (23). A simplified schematic representation of basic human gene therapy methods is described in Figure 13.1. 

Using this approach, several antigens have been introduced into the vaccinia virus. Antigens from HBV, herpes virus, influenza virus, and HIV have been expressed successfully and have been shown to elicit... 

Colman PM (1989) In Krug RM (ed) The Influenza Viruses Influenza Virus Neuraminidase, Enzyme and Antigen. Plenum Press, New York, p. 175... 

Poliomyelitis virus Equine encephalitis virus Influenza virus Phage T3... 

Respiratory virus infections (respiratory syncitial virus [RSV], parainfuenza viruses, influenza viruses and adenoviruses) are all highly contagious and symptomatic individuals should be isolated before virologic confirmation is available. To prevent progression of RSV from the upper to the lower respiratory tract, aerosolized ribavirin may be used alone or in combination with RSV-specific antibodies or palivizumab, an RSV-specific monoclonal antibody (Boeckh et al., 2001). 

Vidarabine is a purine nucleoside analogue active against herpes viruses, influenza viruses, and some RNA viruses. Use of vidarabine for treatment of herpes simplex and varicella-zoster infections has largely been supplanted by acyclovir because of the superior efficacy, fewer adverse effects, and easier administration of the latter agent. Vidarabine has been associated with significant gastrointestinal, neurologic, and hematopoietic toxicities. Patients with renal insuffi-... 

Poliovirus, semilike virus, coronavirus, hepatitis A virus Rabies virus, influenza virus, measles virus Reovirus... 

Ribavirin has antiviral inhibitory activity in vitro against respiratory syncytial virus, influenza virus, and herpes simplex virus. 

Schmidt, Schwarz and colleagues (47,48) further showed that 2F-mannose and 2F-glucose inhibited the biosyntheses of infective Semliki virus and fowl plague virus (influenza virus A) in chick embryo cells eind that of pseudorabies virus in rabbit kidney cells. This was attributed to failure to complete the viral envelope (49)... 

Droplet spread Healthcare workers, patients Staphylococcus aureus Respiratory syncytial virus Influenza virus... 

Povidone-iodine, chlorhexidine gluconate, benzylkonium chloride, alkyl diaminoethylglycine hydrochloride Adenovirus, mumps viras, rotavirus, coxsackievirus, herpesvirus, rubella virus, measles virus, influenza virus, HIV 55... 

Fusion reactions of viruses are mediated by short peptides that fall into two main groups one dependent on a shift to low pH and the other pH-independent [108]. Initial interests here have focused on peptides involved in pH-dependent fusion because of their potential for application in environmentally sensitive, and therefore controllable, model systems. Of the pH-dependent viruses (influenza virus, the vesicular stomatitis virus, the Semliki forest virus and mouse mammary tumor virus [108]), influenza hemagglutinin (HA) is probably the most studied [4]. HA alone is enough to facilitate the fusion of the influenza virus with the host membrane [102,107]. Through the involvement of at least three subunits, it mediates both the initial attachment of the virus to receptors that contain sialic acid [94] and its fusion with the endosomal membrane [57,58]. 

Jedrzejas, M. J., Singh, S. Brouillette, W. J. Air, G. M. Luo, M. A. 1995. Strategy for theoretical binding constant, Ki calculation for neuraminidase aromatic inhibitors, designed on the basis of the active site structure of influenza virus neuraminidase. Proteins Struct. Funct. Genet. 23 (1995) 264-277... 

FIGURE 25 11 Diagram of a cell surface glycoprotein showing the disaccharide unit that IS recognized by an invading influenza virus... 

A second example of up-and-down p sheets is the protein neuraminidase from influenza virus. Here the packing of the sheets is different from that in RBP. They do not form a simple barrel but instead six small sheets, each with four P strands, which are arranged like the blades of a six-bladed propeller. Loop regions between the p strands form the active site in the middle of one side of the propeller. Other similar structures are known with different numbers of the same motif arranged like propellers with different numbers of blades such as the G-proteins discussed in Chapter 13. 

The neuraminidase molecule is a homotetramer made up of four identical polypeptide chains, each of around 470 amino acids the exact number varies depending on the strain of the virus. If influenza virus is treated with the proteolytic enzyme pronase, the head of the neuraminidase, which is soluble, is cleaved off from the stalk projecting from the viral envelope. The soluble head, comprising four subunits of about 400 amino acids each, can be crystallized. 

Figure S.6 Schematic and topological diagrams of the folding motif in neuraminidase from influenza virus The motif is built up from four antiparallel P strands joined by hairpin loops, an up-and-down open P sheet.

Figure S.7 The subunit structure of the neuraminidase headpiece (residues 84-469) from influenza virus is built up from six similar, consecutive motifs of four up-and-down antiparallel fi strands (Figure 5.6). Each such motif has been called a propeller blade and the whole subunit stmcture a six-blade propeller. The motifs are connected by loop regions from p strand 4 in one motif to p strand 1 in the next motif. The schematic diagram (a) is viewed down an approximate sixfold axis that relates the centers of the motifs. Four such six-blade propeller subunits are present in each complete neuraminidase molecule (see Figure 5.8). In the topological diagram (b) the yellow loop that connects the N-terminal P strand to the first P strand of motif 1 is not to scale. In the folded structure it is about the same length as the other loops that connect the motifs. (Adapted from J. Varghese et al.. Nature 303 35-40, 1983.)...

Figure 5.19 Schematic picture of a single subunit of influenza virus hemagglutinin. The two polypeptide chains HAj and HA2 are held together by disulfide bridges.

We have already discussed one envelope protein of influenza virus, neuraminidase, as an example of an up-and-down antiparallel p motif. In the second envelope protein, hemagglutinin, one domain of the polypeptide chain is folded into a jelly roll motif. We shall now look at some other features of hemagglutinin that are important for its biological function. 

Colman, P.M., Varghese, J.N., Laver, W.G. Structure of the catalytic and antigenic sites in influenza virus neuraminidase. Nature 303 41-44, 1983. 

Daniels, R.S., et al. Fusion mutants of the influenza virus hemagglutinin glycoprotein. Cell 40 431-439, 1985. 

Watowich, S.I., et al. Crystal structures of influenza virus haemagglutinin in complex with high affinity receptor analogs. Structure 2 719-731, 1994. 

Wiley, D.C., Skehel, JJ. The structure and function of the hemagglutinin membrane glycoprotein of influenza virus. Annu. Rev. Biochem. 56 365-394, 1987. 

Colman, P.M., et al. Three-dimensional structure of a complex of antibody with influenza virus neuraminidase. Nature 326 358-363, 1987. 

Stern, L.J., Brown, J.H., Jardetzky, T.S., Gorga, J.C., Urban, R.G., Strominger, J.L., Wiley, D.C. Crystal structure of the human class 11 MHC protein HLA-DRl complexed with an influenza virus peptide. Nature 368 215-221,... 

The hemagglutinin protein in influenza virus contains a remarkably long u-helix, with 53 residues. 

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