Identification of the envelope V3 loop as a determinant of a CD4-negative neuronal cell tropism for HIV-1

Virology. 1996 Mar 15;217(2):613-7. doi: 10.1006/viro.1996.0158.


Some neuronal-derived CD4-negative cells are susceptible to infection with human immunodeficiency virus type 1 (HIV-1). Galactosyl ceramide is an alternate receptor for HIV-1 that appears to bind in vitro to the C2, V3, V4, and V5 regions of gp120. Amino acid variation in the V3 loop of HIV-1 affects cellular tropism in CD4-positive cells, but its effect on CD4-negative cells has not been fully analyzed. Here, we describe the effect of amino acid changes in V3 on the HIV-1 infection of a CD4-negative neuronal cell line, SK-N-MC. The sequence of the V3 domain was found to dramatically alter virus infectivity. Furthermore, a gp120 V3 loop neutralizing monoclonal antibody blocked HIV-1 infection of SK-N-MC cells. This data suggests that V3 may also serve as a primary viral determinant for infectivity of CD4-negative cells.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Binding, Competitive
  • CD4 Antigens / analysis
  • Cell Line
  • Galactosylceramides / metabolism
  • HIV Envelope Protein gp120 / chemistry*
  • HIV Infections / microbiology*
  • HIV Infections / pathology
  • HIV-1 / growth & development*
  • Humans
  • Molecular Sequence Data
  • Neurons / microbiology*
  • Receptors, Virus / chemistry*


  • CD4 Antigens
  • Galactosylceramides
  • HIV Envelope Protein gp120
  • Receptors, Virus