Influenza matrix

The induction of CD4+ T helper 1 responses suggests that IRIV could provide adjuvance to the generation of HLA class I-restricted CTL responses. Thus, we addressed the capacity of IRIV to enhance the induction of CTL specific for influenza matrix (IM) 58-66 epitope and Melan-A/Mart-127-35 melanoma-associated epitope. Briefly, CD 14-cells isolated from healthy donor s peripheral blood were cocultured with autologous iDC in presence of peptide and empty IRIV or in presence of peptide alone. 

Figure 5 Immunopotentiating reconstituted influenza virosomes (IRIV) adjuvance on cytotoxic T-cell (CTL) induction. PBMC from a healthy donor were cultured in the presence of influenza matrix (IM)58 66 (A), IMss-eo and control liposomes (B) or IMss-ee and IRIV (C). After a seven-day culture, percentages of IMss-ee speciflc CTL within cultured cells were quantifled by HLA-A0201/IM58 gfi phosphatidylethanolamine tetramer staining (fluorescence 2) and anti CDS fluorescein isothiocyanate staining (fluorescence 1). CTL precursor frequencies detected in IMss-ee and IRIV stimulated cultures within the same experiment are shown in (D). Source From Ref 6.

Figure 7 Immunopotentiating reconstituted influenza virosomes (IRIV) mediated adjuvance in cytotoxic T-cell induction requires CD4+ T cells. CD8+ and CD14+ cells were cultured in the presence of autologous intact or irradiated CD4+ cells. These cultures were stimulated with influenza matrix (IM)58 66 (1 Pg/mL) alone (A) or supplemented with IRIV (1 50) (B). After seven days of incubation both cocultures were restimulated with irradiated IMss-ee pulsed CD14+ cells and cultured for six further days in the presence of interleukin-2 [see Materials and Methods ]. Six days after restimulation, cultures were stained with HLA-A0201 /IM58-66 PE-specilic tetramers and anti-CD8 fluorescein isothiocyanate monoclonal antibodies. Source. From Ref 6.

The immunodominant influenza matrix T cell epitope recognized in human induces influenza protection in HLA-A2/K(b) transgenic mice. Virology 309 320-329... 

Figure 12.3 Colorimetric detection of influenza by sialoside bilayer assembly (2% sialoside lipid 2 and 98% matrix lipid 1). (a) The colorimetric response of the film, supported on a glass microscope slide, is readily visible to the naked eye for quahtative evaluation of the presence of virus. The film on the left (blue) has been exposed to a blank solution of PBS. The film on the right (red) has been exposed to 100 hemagglutinin units (HAU) of vims (CR = 77%). (b) The...

A schematic diagram of an influenza virus particle that illustrates its constituent components and morphology. The surface antigens hemagglutinin and neuraminidase are attached to the lipid and matrix protein shell that encapsulates the eight negative-stranded RNA genes of the virus and associated nucleoprotein and polymerase. 

Mozdzanowska, K., Feng, J., Eid, M et al. (2003) Induction of influenza type A virus-specific resistance by immunization of mice with a synthetic multiple antigenic peptide vaccine that contains ectodomains of matrix protein 2. Vaccine 21, 2616-2626. 

Zhang, M., Zharikova, D., Mozdzanowska, K., Otvos, L Jr., and Gerhard, W. (2006) Fine specificity and sequence of antibodies directed against the ectodomain of matrix protein 2 of influenza A virus. Mol. Immunol. 43, 2195-2206. 

Schreier, P.H. and R. Cortese, 1979. A fast and simple method for sequencing DNA cloned in the single-stranded bacteriophage M13. J. Mol. Biol. 129, 169. Winter. G. and S. Fields, 1980. Cloning of influenza cDNA into M13 the sequence of the RNA segment encoding the A/PR/8/34 matrix protein. Nucleic Acids Res. 8, 1965. 

Resistance Influenza A resistance to amantadine and rimantadine is not a clinical problem as yet, although some viral isolates have shown a high incidence of resistance. Resistance has been shown to be due to a change in one amino acid of the M2 matrix protein. Cross-resistance occurs between the two drugs. 

Negative-strand RNA viruses, 158-163 ebola virus matrix protein/ glycoprotein, 162-163 hemagglutinin-neuraminidase and, 162 influenza A and, 158-163 Ml and, 161 Ms and, 161-162 neuraminidase and, 161 paramyxovirus fusion protein and, 162 Neuraminidase, negative-strand RNA viruses and, 161... 

The influenza virus is an RNA-(—)- virus and possesses its own RNA polymerase enzyme. The complete RNA genome codes for eight proteins - two structural (matrix) proteins M, and M2, haemagglutinin, and neuraminidase and four proteins involved in replication, three of which make up the polymerase enzyme. Substrates for this are the usual ribonucleosides and there has been some success with the use of nucleoside analogues as inhibitors of the enzyme. The drug ribavirin has been the most successful, although this has to be administered by aerosol. These days, its major use is for the treatment of infections caused by respiratory syncytial viruses (especially in children), since these can cause long-term morbidity. 

Amantadine (Scheme 8,3), and rimantadine (Scheme 8,4) are active against influenza A viruses. The action of these closely related agents is complex and incompletely understood, but they are believed to block cellular membrane ion channels [37,38], Both drugs target the influenza A matrix protein (M2). Drug-treated cells are unable to lower the pH of the endosomal compartment (a function normally controlled by the M2 gene product), a process which is essential to induce conformational changes in the HA protein to permit membrane fusion. 

Elleman, C.J. and Barclay, W.S. (2004) The Ml matrix protein controls the filamentous phenotype of influenza A virus. Virology, 321, 144-153. 

---