Moscona, A. Neuraminidase inhibitors for influenza. N. Engl. J. Med. 353 (2005) 1363–1367. http://dx.doi.org/10.1056/NEJMra050740
 Matrosovich, M.N., Matrosovitch, T.Y., Gray, T, Roberts, N.A. and Klenk, H.D. Neuraminidase is important for the initiation of influenza virus infection in human airway epithelium. J. Virol. 78 (2004) 12665–12667. http://dx.doi.org/10.1128/JVI.78.22.12665-12667.2004
 Gubareva, L.V., Kaiser, L. and Hayden, F.G. Influenza virus neuraminidase inhibitors. Lancet 355 (2000) 827–835. http://dx.doi.org/10.1016/S0140-6736(99)11433-8
 Englund, J.A. Antiviral therapy of influenza. Sem. in Ped. Infect. Dis. 13 (2002) 120–128. http://dx.doi.org/10.1053/spid.2002.122999
 Stiver, G. The treatment of influenza with antiviral drugs. CMAJ 168 (2003) 49–57.
 Colman, P.M. A novel approach to antiviral therapy for influenza. J. Antimicrob. Chemother. 44 (1999) 17–22. http://dx.doi.org/10.1093/jac/44.suppl_2.17
 Brandtzaeg, P., Farstad, I.N., Johansen, F.E., Morton, H.C., Norderhaug, I.N. and Yamanaka, T. The B-cell system of human mucosae and exocrine glands. Immunol. Rev. 171 (1999) 45–87. http://dx.doi.org/10.1111/j.1600-065X.1999.tb01342.x
 Tomana, M., Kulhavy, R. and Mestecky, J. Receptor-mediated binding and uptake of IgA by human liver. Gastroenterology 94 (1988) 762–770.
 Groh, V., Porcelli, S., Fabbi, M., Lanier, L.L., Picker, L.J., Anderson, T., Warnke, R.A., Bhan, A.K., Strominger, J.L. and Brenner, M.B. Human lymphocyes bearing T cell receptor gamma/delta are phenotypically diverse and evenly distributed throughout the lymphoid system. J. Exp. Med. 169 (1989) 1277–1294. http://dx.doi.org/10.1084/jem.169.4.1277
 Spencer, J., Isaacson, P.G., Diss, T.C. and MacDonald, T.T. Expression of disulfide-linked and non-disulfide-linked forms of the T cell receptor gamma/delta heterodimer in human intestinal intraepithelial lymphocytes. Eur. J. Immunol. 19 (1989) 1335–1338.
 Deusch, K., Luling, F., Reich, K., Classen, M., Wagner, H. and Pfeffer, K.A major fraction of human intraepithelial lymphocytes simultaneously expresses the gamma/delta T cell receptor, the CD8 accessory molecule and preferentially uses the V delta1 gene segment. Eur. J. Immunol. 21 (1991) 1053–1059.
 Jones, W.M., Walcheck, B. and Jutila, M.A. Generation of a new gamma/delta T cell-specific monoclonal antibody (GD3.5). J. Immunol. 156 (1996) 3772–3779.
 Floyd, H., Nitschke, L. and Crocker, P.R. A novel subset of murine B cells that expresses unmasked forms of CD22 is enriched in the bone marrow: Implications for B-cell homing to the bone marrow. Immunology 101 (2000) 342–347. http://dx.doi.org/10.1046/j.1365-2567.2000.00103.x
 Nitschke, L., Floyd, H. and Ferguson, D.J., Identification of CD22 ligands on CD22 bone marrow sinusoidal endothelium implicated in CD22-dependent homing of recirculating B-cells. J. Exp. Med. 189 (1999) 1513–1518. http://dx.doi.org/10.1084/jem.189.9.1513
 Reinholdt, J., Tomana, M. and Mortensen, S.B. Molecular aspects of IgA degredation by oral streptococci. Infect. Immunol. 58 (1990) 1186–1194.
 Kast R.E. A theory of lymphocyte blast transformation and malignant change based on proteolytic cleavage of the trigger peptide: The detendomer. Oncology 29 (1974) 249–264. http://dx.doi.org/10.1159/000224907
 Kast, R.E. Lymphocytes and cells in malignant transformation. Oncology 32 (1975) 175–189.
 Gronbaek Frandsen, E.V. Bacterial degradation of IgA1 in relation to periodontal disease. APMIS (Suppl) 87 (1999) 1–54.
 King, S.J., Hippe, K.R., Gould, J.M., Bae, D., Peterson, S., Cline, R.T., Fasching, C., Janoff, E.N. and Weiser, J.N. Phase variable desialylation of host proteins that bind to Streptococcus pneumoniae in vivo and protect the airway. Mol. Microbiol. 54 (2004) 159–171. http://dx.doi.org/10.1111/j.1365-2958.2004.04252.x
 Kannagi, R. Regulatory roles of carbohydrate ligands for selectins in the homing of lymphocytes. Curr. Opin. Struct. Biol. 12 (2002) 599–608. http://dx.doi.org/10.1016/S0959-440X(02)00365-2
 Glezen, W.P., Payne, A.A. and Snyder, D.N. Mortality and influenza. J. Infect. Dis. 146 (1982) 313–321.
 Simonsen, L, Fukada, K. and Schonberger, L.B. The impact of influenza epidemics on hospitalizations. J. Infect. Dis. 181 (2000) 831–837. http://dx.doi.org/10.1086/315320
 Simonsen, L. The global impact of influenza on morbidity and mortality. Vaccine 17 (Suppl 1) (1999) S3–10. http://dx.doi.org/10.1016/S0264-410X(99)00099-7
 McCullers, J.A. and Bartmess, K.C. Role of neauraminidase in lethal synergism between influenza virus and streptococcus pneumoniae. J. Infect. Dis. 187 (2003) 1000–1009. http://dx.doi.org/10.1086/368163
 McCullers, J.A. Effect of antiviral treatment on the outcome of secondary bacterial pneumonia after influenza. J. Infect. Dis. 190 (2004) 519–526. http://dx.doi.org/10.1086/421525
 Kaiser, L., Wat, C., Mills, T., Mahoney, P., Ward, P. and Hayden, F. Impact of oseltamivir treatment on influenza-related lower respiratory tract complications and hospitalizations. Arch. Intern. Med. 163 (2003) 1667–1672. http://dx.doi.org/10.1001/archinte.163.14.1667
 Kaiser, L., Keene, O.N. and Hammond, J.M. Impact of zanamivir on antibiotic use for respiratory events following acute influenza in adolescents and adults. Arch Intern Med 160 (2000) 3234–3240. http://dx.doi.org/10.1001/archinte.160.21.3234
 Treanor, J.J., Hayden, F.G., Vrooman, P.S., Barbarash, R., Bettis, R., Riff, D., Singh, S., Kinnersley, N., Ward, P. and Mills, R.G. Efficacy and safety of oral neuraminidase Inhibitor oseltamivir in treating acute influenza: A randomized controlled trial. JAMA 283 (2000) 1016–1024. http://dx.doi.org/10.1001/jama.283.8.1016
 Monto, A.S., Webster, A. and Keene, O. Randomized, placebo-controlled studies of inhaled zanamivir in the treatment of influenza A and B: Pooled efficacy analysis. J. Antimicrob. Chemother. 44 (1999) 23–29. http://dx.doi.org/10.1093/jac/44.suppl_2.23
 Peltola, V.T., Murti, K.G. and McCullers, J.A. Influenza virus neuraminidase contributes to secondary bacterial pneumonia. J Infect Dis. 192 (2005) 249–257. http://dx.doi.org/10.1086/430954
 Peltola, V.T. and McCullers, J.A. Respiratory viruses predisposing to bacterial infections: role of neuraminidase. Pediatr. Infect. Dis. J. 23 (Suppl.1) (2004) S87–97. http://dx.doi.org/10.1097/01.inf.0000107021.66218.ec
 Yen, H.L., Herlocher, L.M., Hoffmann, E., Matrosovich, M.N., Monto, A.S., Webster, R.G. and Govorkova, E.A. Neuraminidase inhibitor-resistant influenza viruses may differ substantially in fitness and transmissibility. Antimicrob. Agents Chemother. 49 (2005) 4075–4084. http://dx.doi.org/10.1128/AAC.49.10.4075-4084.2005
 Roberts, N. Treatment of influenza with neuraminidase inhibitors: Virological implications. Phil. Trans. R. Soc. Lond. 356 (2001) 1895–1897. http://dx.doi.org/10.1098/rstb.2001.1002
 Wakai, K., Nakai, S., Matsuo, S., Kawamura, T., Hotta, N., Maeda, K. and Ohno, Y. Risk factors for IgA nephropathy: A case-control study with incident cases in Japan. Nephron 90 (2002) 16–23. http://dx.doi.org/10.1159/000046309
 Xu, L.X. and Zhao, M.H. Aberrantly glycosylated serum IgA1 are closely associated with pathologic phenotypes of IgA nephropathy. Kidney Int. 68 (2005) 167–172. http://dx.doi.org/10.1111/j.1523-1755.2005.00390.x
 Altschuler, E.L., Bhatia, A. and Kast, R.E. Consideration of use of neuraminidase inhibitors such as oseltamivir and zanamivir in IgA nephropathy. Kidney Int. 68 (2005) 2910–2911. http://dx.doi.org/10.1111/j.1523-1755.2005.00583_7.x
Volume 18 (2013)
Volume 17 (2012)
Volume 16 (2011)
Volume 15 (2010)
Volume 14 (2009)
Volume 13 (2008)
Volume 12 (2007)
Most Downloaded Articles
- R proteins as fundamentals of plant innate immunity by Głowacki, Sylwester/ Macioszek, Violetta and Kononowicz, Andrzej
- Telomerase and its extracurricular activities by Jaiswal, Rishi/ Kumar, Pramod and Yadava, Pramod
- Puma, a critical mediator of cell death — one decade on from its discovery by Hikisz, Paweł and Kiliańska, Zofia
- Tubulin-interactive stilbene derivatives as anticancer agents by Mikstacka, Renata/ Stefański, Tomasz and Różański, Jakub
- The differentiation of human placenta-derived mesenchymal stem cells into dopaminergic cells in vitro by Chen, Li/ He, Dong-Mei and Zhang, Yuan
How influenza’s neuraminidase promotes virulence and creates localized lung mucosa immunodeficiency
1Ohio State University
2University of Vermont
© 2006 Versita Warsaw. This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License. (CC BY-NC-ND 3.0)
Citation Information: Cellular and Molecular Biology Letters. Volume 12, Issue 1, Pages 111–119, ISSN (Online) 1689-1392, DOI: 10.2478/s11658-006-0055-x, November 2006
- Published Online:
Neuraminidase (NA) is an enzyme coded for by the genome of influenza critical for its pathogenicity and survival. Three currently accepted roles for this NA in promoting influenza virulence are: 1. NA cleaves newly formed virus particles from the host cell membrane. Without NA, newly formed virus would remain attached to the cell within which it was produced. 2. NA prevents newly released virus particles from aggregating to each other, preventing clumping that would reduce dissemination. 3. NA promotes viral penetration of sialic acid-rich mucin that bathes and protects respiratory epithelium through which the virus must spread and replicate. We outline here previous research evidence of two further, albeit hypothetical, functions of NA that together could cause disruption the mucosa-IgA axis, creating localized partial immunosuppressed state, enhancing both influenza infection itself and secondary bacterial pneumonia: 4. IgA provides primary immunoglobulin defense of mucosal surfaces. The hinge region of IgA is normally sialylated. IgA denuded of sialic acid is recognized, bound, and cleared by hepatic asialoglycoprotein receptor (ASGPR). Thus, IgA exposed to free NA would be so denuded and have increased hepatic clearance. 5. NA removes sialic acid moieties from mucosa-residing gamma/delta T cells or IgA producing B cells. Previous work indicates desialylation of these lymphocytes' outer cell membrane results in altered homing, to bone marrow, away from mucosa. Currently marketed NA inhibitors oseltamivir (Tamiflu) and zanamivir (Relenza) are FDA approved in USA for influenza prophylaxis and treatment. These NA inhibitors lower incidence of secondary bacterial infection in cases where an influenza infection occurs despite their use. Moreover, they are ameliorative in patients with secondary bacterial infections treated with antibiotics, a benefit that surpasses the treatment of antibiotics alone. We interpret these last two points as indicating our ascription of localized immunosuppression to influenza's NA could be correct and lead to new treatments of infections generally.