The stem of vesicular stomatitis virus G can be replaced with the HIV-1 Env membrane-proximal external region without loss of G function or membrane-proximal external region antigenic properties

AIDS Res Hum Retroviruses. 2014 Nov;30(11):1130-44. doi: 10.1089/AID.2013.0206. Epub 2014 Apr 9.


The structure of the HIV-1 envelope membrane-proximal external region (MPER) is influenced by its association with the lipid bilayer on the surface of virus particles and infected cells. To develop a replicating vaccine vector displaying MPER sequences in association with membrane, Env epitopes recognized by the broadly neutralizing antibodies 2F5, 4E10, or both were grafted into the membrane-proximal stem region of the vesicular stomatitis virus (VSV) glycoprotein (G). VSV encoding functional G-MPER chimeras based on G from the Indiana or New Jersey serotype propagated efficiently, although grafting of both epitopes (G-2F5-4E10) modestly reduced replication and resulted in the acquisition of one to two adaptive mutations in the grafted MPER sequence. Monoclonal antibodies 2F5 and 4E10 efficiently neutralized VSV G-MPER vectors and bound to virus particles in solution, indicating that the epitopes were accessible in the preattachment form of the G-MPER chimeras. Overall, our results showed that the HIV Env MPER could functionally substitute for the VSV G-stem region implying that both perform similar functions even though they are from unrelated viruses. Furthermore, we found that the MPER sequence grafts induced low but detectable MPER-specific antibody responses in rabbits vaccinated with live VSV, although additional vector and immunogen modifications or use of a heterologous prime-boost vaccination regimen will be required to increase the magnitude of the immune response.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Neutralizing / immunology
  • Female
  • HIV Antibodies / immunology*
  • Membrane Glycoproteins / genetics*
  • Membrane Glycoproteins / immunology
  • Membrane Glycoproteins / metabolism*
  • Rabbits
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology
  • Recombinant Proteins / metabolism
  • Vesiculovirus / genetics
  • Vesiculovirus / growth & development
  • Vesiculovirus / immunology
  • Vesiculovirus / physiology*
  • Viral Envelope Proteins / genetics*
  • Viral Envelope Proteins / immunology
  • Viral Envelope Proteins / metabolism*
  • Virus Replication
  • env Gene Products, Human Immunodeficiency Virus / genetics*
  • env Gene Products, Human Immunodeficiency Virus / immunology
  • env Gene Products, Human Immunodeficiency Virus / metabolism*


  • Antibodies, Neutralizing
  • G protein, vesicular stomatitis virus
  • HIV Antibodies
  • Membrane Glycoproteins
  • Recombinant Proteins
  • Viral Envelope Proteins
  • env Gene Products, Human Immunodeficiency Virus