Antibody-induced internalization of the human respiratory syncytial virus fusion protein

      Research output: Research - peer-reviewArticle

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      Antibody-induced internalization of the human respiratory syncytial virus fusion protein. / Leemans, Alexander; De Schryver, M; Van der Gucht, W; Heykers, A; Pintelon, I; Hotard, A L; Moore, M.L.; Melero, J A; McLellan, J S; Graham, Barney; Broadbent, L; Power, U F; Caljon, G; Cos, P; Maes, L; Delputte, P.

      In: Journal of Virology, 03.05.2017.

      Research output: Research - peer-reviewArticle

      Harvard

      Leemans, A, De Schryver, M, Van der Gucht, W, Heykers, A, Pintelon, I, Hotard, AL, Moore, ML, Melero, JA, McLellan, JS, Graham, B, Broadbent, L, Power, UF, Caljon, G, Cos, P, Maes, L & Delputte, P 2017, 'Antibody-induced internalization of the human respiratory syncytial virus fusion protein' Journal of Virology. DOI: 10.1128/JVI.00184-17

      APA

      Leemans, A., De Schryver, M., Van der Gucht, W., Heykers, A., Pintelon, I., Hotard, A. L., ... Delputte, P. (2017). Antibody-induced internalization of the human respiratory syncytial virus fusion protein. Journal of Virology. DOI: 10.1128/JVI.00184-17

      Vancouver

      Leemans A, De Schryver M, Van der Gucht W, Heykers A, Pintelon I, Hotard AL et al. Antibody-induced internalization of the human respiratory syncytial virus fusion protein. Journal of Virology. 2017 May 3. Available from, DOI: 10.1128/JVI.00184-17

      Author

      Leemans, Alexander ; De Schryver, M ; Van der Gucht, W ; Heykers, A ; Pintelon, I ; Hotard, A L ; Moore, M.L. ; Melero, J A ; McLellan, J S ; Graham, Barney ; Broadbent, L ; Power, U F ; Caljon, G ; Cos, P ; Maes, L ; Delputte, P. / Antibody-induced internalization of the human respiratory syncytial virus fusion protein. In: Journal of Virology. 2017

      Bibtex

      @article{d2e74556d65349649092aad2b6e4b107,
      title = "Antibody-induced internalization of the human respiratory syncytial virus fusion protein",
      abstract = "Respiratory syncytial virus (RSV) infections remain a major cause of respiratory disease and hospitalizations among infants. Infection recurs frequently and establishes a weak and short-lived immunity. To date, RSV immunoprophylaxis and vaccine research is mainly focused on the RSV fusion (F) protein, but a vaccine remains elusive. The RSV F protein is a highly conserved surface glycoprotein and the main target of neutralizing antibodies induced by natural infection. Here, we analyzed an internalization process of antigen-antibody complexes after binding of RSV-specific antibodies to RSV antigens expressed on the surface of infected cells. The RSV F protein and attachment (G) protein were found to be internalized in both infected and transfected cells after the addition of either RSV-specific polyclonal antibodies (pAbs) or RSV glycoprotein-specific monoclonal antibodies (mAbs), as determined by indirect immunofluorescence staining and flow-cytometric analysis. Internalization experiments with different cell lines, well-differentiated primary bronchial epithelial cells (WD-PBECs) and RSV isolates suggest that antibody-internalization can be considered as a general feature of RSV. More specifically for RSV F, the mechanism of internalization was shown to be clathrin-dependent. All RSV F-targeted mAbs tested, regardless of their epitopes, induced internalization of RSV F. No differences could be observed between the different mAbs, indicating that RSV F internalization was epitope-independent. Since this process can be either antiviral, by affecting virus assembly and production, or beneficial for the virus, by limiting the efficacy of antibodies and effector mechanism, further research is required to determine the extent to which this occurs in vivo and how this might impact RSV replication.IMPORTANCE Current research into the development of new immunoprophylaxis and vaccines is mainly focused on the RSV F protein since, among others, RSV F-specific antibodies are able to protect infants from severe disease, if administered prophylactically. However, antibody responses established after natural RSV infections are poorly protective against reinfection and high levels of antibodies do not always correlate with protection. Therefore, RSV might be capable of interfering, at least partially, with antibody-induced neutralization. In this study, a process through which surface-expressed RSV F proteins are internalized after interaction with RSV-specific antibodies is described. One the one hand, this antigen-antibody complex internalization could result in an antiviral effect, since it may interfere with virus particle formation and virus production. On the other hand, this mechanism may also reduce the efficacy of antibody-mediated effector mechanisms towards infected cells.",
      keywords = "Journal Article",
      author = "Alexander Leemans and {De Schryver}, M and {Van der Gucht}, W and A Heykers and I Pintelon and Hotard, {A L} and M.L. Moore and Melero, {J A} and McLellan, {J S} and Barney Graham and L Broadbent and Power, {U F} and G Caljon and P Cos and L Maes and P Delputte",
      note = "Copyright © 2017 American Society for Microbiology.",
      year = "2017",
      month = "5",
      doi = "10.1128/JVI.00184-17",
      journal = "Journal of Virology",
      issn = "0022-538X",
      publisher = "American Society for Microbiology",

      }

      RIS

      TY - JOUR

      T1 - Antibody-induced internalization of the human respiratory syncytial virus fusion protein

      AU - Leemans,Alexander

      AU - De Schryver,M

      AU - Van der Gucht,W

      AU - Heykers,A

      AU - Pintelon,I

      AU - Hotard,A L

      AU - Moore,M.L.

      AU - Melero,J A

      AU - McLellan,J S

      AU - Graham,Barney

      AU - Broadbent,L

      AU - Power,U F

      AU - Caljon,G

      AU - Cos,P

      AU - Maes,L

      AU - Delputte,P

      N1 - Copyright © 2017 American Society for Microbiology.

      PY - 2017/5/3

      Y1 - 2017/5/3

      N2 - Respiratory syncytial virus (RSV) infections remain a major cause of respiratory disease and hospitalizations among infants. Infection recurs frequently and establishes a weak and short-lived immunity. To date, RSV immunoprophylaxis and vaccine research is mainly focused on the RSV fusion (F) protein, but a vaccine remains elusive. The RSV F protein is a highly conserved surface glycoprotein and the main target of neutralizing antibodies induced by natural infection. Here, we analyzed an internalization process of antigen-antibody complexes after binding of RSV-specific antibodies to RSV antigens expressed on the surface of infected cells. The RSV F protein and attachment (G) protein were found to be internalized in both infected and transfected cells after the addition of either RSV-specific polyclonal antibodies (pAbs) or RSV glycoprotein-specific monoclonal antibodies (mAbs), as determined by indirect immunofluorescence staining and flow-cytometric analysis. Internalization experiments with different cell lines, well-differentiated primary bronchial epithelial cells (WD-PBECs) and RSV isolates suggest that antibody-internalization can be considered as a general feature of RSV. More specifically for RSV F, the mechanism of internalization was shown to be clathrin-dependent. All RSV F-targeted mAbs tested, regardless of their epitopes, induced internalization of RSV F. No differences could be observed between the different mAbs, indicating that RSV F internalization was epitope-independent. Since this process can be either antiviral, by affecting virus assembly and production, or beneficial for the virus, by limiting the efficacy of antibodies and effector mechanism, further research is required to determine the extent to which this occurs in vivo and how this might impact RSV replication.IMPORTANCE Current research into the development of new immunoprophylaxis and vaccines is mainly focused on the RSV F protein since, among others, RSV F-specific antibodies are able to protect infants from severe disease, if administered prophylactically. However, antibody responses established after natural RSV infections are poorly protective against reinfection and high levels of antibodies do not always correlate with protection. Therefore, RSV might be capable of interfering, at least partially, with antibody-induced neutralization. In this study, a process through which surface-expressed RSV F proteins are internalized after interaction with RSV-specific antibodies is described. One the one hand, this antigen-antibody complex internalization could result in an antiviral effect, since it may interfere with virus particle formation and virus production. On the other hand, this mechanism may also reduce the efficacy of antibody-mediated effector mechanisms towards infected cells.

      AB - Respiratory syncytial virus (RSV) infections remain a major cause of respiratory disease and hospitalizations among infants. Infection recurs frequently and establishes a weak and short-lived immunity. To date, RSV immunoprophylaxis and vaccine research is mainly focused on the RSV fusion (F) protein, but a vaccine remains elusive. The RSV F protein is a highly conserved surface glycoprotein and the main target of neutralizing antibodies induced by natural infection. Here, we analyzed an internalization process of antigen-antibody complexes after binding of RSV-specific antibodies to RSV antigens expressed on the surface of infected cells. The RSV F protein and attachment (G) protein were found to be internalized in both infected and transfected cells after the addition of either RSV-specific polyclonal antibodies (pAbs) or RSV glycoprotein-specific monoclonal antibodies (mAbs), as determined by indirect immunofluorescence staining and flow-cytometric analysis. Internalization experiments with different cell lines, well-differentiated primary bronchial epithelial cells (WD-PBECs) and RSV isolates suggest that antibody-internalization can be considered as a general feature of RSV. More specifically for RSV F, the mechanism of internalization was shown to be clathrin-dependent. All RSV F-targeted mAbs tested, regardless of their epitopes, induced internalization of RSV F. No differences could be observed between the different mAbs, indicating that RSV F internalization was epitope-independent. Since this process can be either antiviral, by affecting virus assembly and production, or beneficial for the virus, by limiting the efficacy of antibodies and effector mechanism, further research is required to determine the extent to which this occurs in vivo and how this might impact RSV replication.IMPORTANCE Current research into the development of new immunoprophylaxis and vaccines is mainly focused on the RSV F protein since, among others, RSV F-specific antibodies are able to protect infants from severe disease, if administered prophylactically. However, antibody responses established after natural RSV infections are poorly protective against reinfection and high levels of antibodies do not always correlate with protection. Therefore, RSV might be capable of interfering, at least partially, with antibody-induced neutralization. In this study, a process through which surface-expressed RSV F proteins are internalized after interaction with RSV-specific antibodies is described. One the one hand, this antigen-antibody complex internalization could result in an antiviral effect, since it may interfere with virus particle formation and virus production. On the other hand, this mechanism may also reduce the efficacy of antibody-mediated effector mechanisms towards infected cells.

      KW - Journal Article

      U2 - 10.1128/JVI.00184-17

      DO - 10.1128/JVI.00184-17

      M3 - Article

      JO - Journal of Virology

      T2 - Journal of Virology

      JF - Journal of Virology

      SN - 0022-538X

      ER -

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