Kaw, Sheetal, Ananth, Swetha, Tsopoulidis, Nikolaos, Morath, Katharina, Coban, Bahar M., Hohenberger, Ralph, Bulut, Olcay C., Klein, Florian, Stolp, Bettina and Fackler, Oliver T. . Expression of HIV-1 pathogenesis factor NEF in CD4 T cells impairs antigen-specific B-cell function. Embo J.. HOBOKEN: WILEY. ISSN 1460-2075

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Kaw, SheetalUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ananth, SwethaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tsopoulidis, NikolaosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Morath, KatharinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Coban, Bahar M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hohenberger, RalphUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bulut, Olcay C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klein, FlorianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stolp, BettinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fackler, Oliver T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-312194
DOI: 10.15252/embj.2020105594
Journal or Publication Title: Embo J.
Publisher: WILEY
Place of Publication: HOBOKEN
ISSN: 1460-2075
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
BROADLY NEUTRALIZING ANTIBODIES; DOWN-REGULATION; PLASMA-CELL; INFECTION; RESPONSES; SURFACE; MEMORY; REPLICATION; VACCINATION; INTERFERESMultiple languages
Biochemistry & Molecular Biology; Cell BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/31219

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