HIV-1 evades virus-specific IgG2 and IgA responses by targeting systemic and intestinal B cells via long-range intercellular conduits Academic Article uri icon


MeSH Major

  • B-Lymphocytes
  • Cell Communication
  • HIV Antibodies
  • HIV-1
  • Immunoglobulin A
  • Immunoglobulin G
  • nef Gene Products, Human Immunodeficiency Virus


  • Contact-dependent communication between immune cells generates protection but also facilitates viral spread. Here we found that macrophages formed long-range actin-propelled conduits in response to negative factor (Nef), a human immunodeficiency virus type 1 (HIV-1) protein with immunosuppressive functions. Conduits attenuated immunoglobulin G2 (IgG2) and IgA class switching in systemic and intestinal lymphoid follicles by shuttling Nef from infected macrophages to B cells through a guanine-exchange factor-dependent pathway involving the amino-terminal anchor, central core and carboxy-terminal flexible loop of Nef. By showing stronger virus-specific IgG2 and IgA responses in patients with Nef-deficient virions, our data suggest that HIV-1 exploits intercellular 'highways' as a 'Trojan horse' to deliver Nef to B cells and evade humoral immunity systemically and at mucosal sites of entry.

publication date

  • August 3, 2009



  • Academic Article



  • eng

PubMed Central ID

  • PMC2784687

Digital Object Identifier (DOI)

  • 10.1038/ni.1753

PubMed ID

  • 19648924

Additional Document Info

start page

  • 1008

end page

  • 17


  • 10


  • 9