1. HIV-1 infection of CD4 T cells impairs antigen-specific B cell function.
- Author
-
Kaw S, Ananth S, Tsopoulidis N, Morath K, Coban BM, Hohenberger R, Bulut OC, Klein F, Stolp B, and Fackler OT
- Subjects
- Animals, HEK293 Cells, HIV-1, Humans, Immune Evasion immunology, Lymphocyte Activation, Male, Mice, Mice, Inbred C57BL, B-Lymphocytes immunology, CD4-Positive T-Lymphocytes immunology, HIV Infections immunology
- Abstract
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., (© 2020 The Authors. Published under the terms of the CC BY NC ND 4.0 license.)
- Published
- 2020
- Full Text
- View/download PDF