Beyond Viral Neutralization

George K. Lewis, Marzena Pazgier, David T. Evans, Guido Ferrari, Stylianos Bournazos, Matthew S. Parsons, Nicole F. Bernard, Andrés Finzi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

It has been known for more than 30 years that HIV-1 infection drives a very potent B cell response resulting in the production of anti-HIV-1 antibodies targeting several viral proteins, particularly its envelope glycoproteins (Env). Env epitopes are exposed on the surfaces of viral particles and infected cells where they are targets of potentially protective antibodies. These antibodies can interdict infection by neutralization and there is strong evidence suggesting that Fc-mediated effector function can also contribute to protection. Current evidence suggests that Fc-mediated effector function plays a role in protection against infection by broadly neutralizing antibodies and it might be important for protection by non-neutralizing antibodies. Fc-mediated effector function includes diverse mechanisms such as antibody-dependent cellular cytotoxicity (ADCC), antibody-mediated complement activation, antibody-dependent cellular phagocytosis, antibody-dependent cell-mediated virus inhibition, antibody-mediated trancytosis inhibition, and antibody-mediated virus opsonization. All these functions could be beneficial in fighting viral infections, including HIV-1. In this perspective, we discuss the latest developments in ADCC research discussed at the HIVR4P satellite session on non-neutralizing antibodies, with emphasis on the mechanisms of ADCC resistance used by HIV-1, the structural basis of epitopes recognized by antibodies that mediate ADCC, natural killer-cell education and ADCC, and murine models to study ADCC against HIV-1.

Original languageEnglish
Pages (from-to)760-764
Number of pages5
JournalAIDS Research and Human Retroviruses
Volume33
Issue number8
DOIs
StatePublished - Aug 2017
Externally publishedYes

Keywords

  • ADCC
  • Env
  • Fc
  • HIV-1
  • KIR
  • NK
  • humanized mouse models
  • neutralization
  • non-neutralizing antibodies

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