Structural insights into key sites of vulnerability on HIV-1 Env and influenza HA

Immunol Rev. 2012 Nov;250(1):180-98. doi: 10.1111/imr.12005.


Human immunodeficiency virus-1 (HIV-1) envelope protein (Env) and influenza hemagglutinin (HA) are the surface glycoproteins responsible for viral entry into host cells, the first step in the virus life cycle necessary to initiate infection. These glycoproteins exhibit a high degree of sequence variability and glycosylation, which are used as strategies to escape host immune responses. Nonetheless, antibodies with broadly neutralizing activity against these viruses have been isolated that have managed to overcome these barriers. Here, we review recent advances in the structural characterization of these antibodies with their viral antigens that defines a few sites of vulnerability on these viral spikes. These broadly neutralizing antibodies tend to focus their recognition on the sites of similar function between the two viruses: the receptor-binding site and membrane fusion machinery. However, some sites of recognition are unique to the virus neutralized, such as the dense shield of oligomannose carbohydrates on HIV-1 Env. These observations are discussed in the context of structure-based design strategies to aid in vaccine design or development of antivirals.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • AIDS Vaccines / chemistry
  • AIDS Vaccines / immunology
  • Antibodies, Neutralizing / chemistry*
  • Antibodies, Neutralizing / immunology
  • Antibodies, Neutralizing / pharmacology
  • Antigenic Variation
  • Gene Products, env / antagonists & inhibitors
  • Gene Products, env / chemistry*
  • Gene Products, env / immunology
  • HIV Antibodies / chemistry*
  • HIV Antibodies / immunology
  • HIV Antibodies / pharmacology
  • HIV-1 / drug effects
  • HIV-1 / immunology
  • Hemagglutinin Glycoproteins, Influenza Virus / chemistry*
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology
  • Hemagglutinin Glycoproteins, Influenza Virus / metabolism
  • Humans
  • Influenza A virus / drug effects
  • Influenza A virus / immunology
  • Influenza Vaccines / chemistry
  • Influenza Vaccines / immunology
  • Models, Molecular
  • Receptors, Virus / antagonists & inhibitors*
  • Receptors, Virus / immunology
  • Species Specificity
  • Structural Homology, Protein
  • Virus Internalization / drug effects


  • AIDS Vaccines
  • Antibodies, Neutralizing
  • Gene Products, env
  • HIV Antibodies
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Influenza Vaccines
  • Receptors, Virus
  • hemagglutinin, human influenza A virus