Human beta defensin 2 selectively inhibits HIV-1 in highly permissive CCR6+CD4+ T cells
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AbstractChemokine receptor type 6 (CCR6)+CD4+ T cells are preferentially infected and depleted during HIV disease progression, but are preserved in non-progressors. CCR6 is expressed on a heterogeneous population of memory CD4+ T cells that are critical to mucosal immunity. Preferential infection of these cells is associated, in part, with high surface expression of CCR5, CXCR4, and α4β7. In addition, CCR6+CD4+ T cells harbor elevated levels of integrated viral DNA and high levels of proliferation markers. We have previously shown that the CCR6 ligands MIP-3? and human beta defensins inhibit HIV replication. The inhibition required CCR6 and the induction of APOBEC3G. Here, we further characterize the induction of apolipoprotein B mRNA editing enzyme (APOBEC3G) by human beta defensin 2. Human beta defensin 2 rapidly induces transcriptional induction of APOBEC3G that involves extracellular signal-regulated kinases 1/2 (ERK1/2) activation and the transcription factors NFATc2, NFATc1, and IRF4. We demonstrate that human beta defensin 2 selectively protects primary CCR6+CD4+ T cells infected with HIV-1. The selective protection of CCR6+CD4+ T cell subsets may be critical in maintaining mucosal immune function and preventing disease progression. Copyright 2017 by the authors.
SponsorsThis work was supported by the National Institute of Neurological Disorders And Stroke award R01NS066842 to Alfredo Garzino-Demo. Aaron Christensen-Quick was a trainee under Institutional Training Grant 1T32AI095190-01A1 from the National Institute of Allergy and Infectious Diseases. Mark K. Lafferty was a trainee under Institutional Training Grant T32AI007540 from the National Institute of Allergy and Infectious Diseases.
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85019636317&doi=10.3390%2fv9050111&partnerID=40&md5=23df3fb82bb8be8768082671fe107114; http://hdl.handle.net/10713/11300
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