HIV-1 infection of CD4 T cells impairs antigen-specific B cell function

EMBO J. 2020 Dec 15;39(24):e105594. doi: 10.15252/embj.2020105594. Epub 2020 Nov 4.


Failures to produce neutralizing antibodies upon HIV-1 infection result in part from B-cell dysfunction due to unspecific B-cell activation. How HIV-1 affects antigen-specific B-cell functions remains elusive. Using an adoptive transfer mouse model and ex vivo HIV infection of human tonsil tissue, we found that expression of the HIV-1 pathogenesis factor NEF in CD4 T cells undermines their helper function and impairs cognate B-cell functions including mounting of efficient specific IgG responses. NEF interfered with T cell help via a specific protein interaction motif that prevents polarized cytokine secretion at the T-cell-B-cell immune synapse. This interference reduced B-cell activation and proliferation and thus disrupted germinal center formation and affinity maturation. These results identify NEF as a key component for HIV-mediated dysfunction of antigen-specific B cells. Therapeutic targeting of the identified molecular surface in NEF will facilitate host control of HIV infection.

Keywords: B-cell dysfunction; HIV-1 infection; NEF; immunological synapse; intravital imaging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • HEK293 Cells
  • HIV Infections / immunology*
  • HIV-1
  • Humans
  • Immune Evasion / immunology
  • Lymphocyte Activation
  • Male
  • Mice
  • Mice, Inbred C57BL

Associated data

  • GEO/GSE156100