Human Beta Defensin 2 Selectively Inhibits HIV-1 in Highly Permissive CCR6⁺CD4⁺ T Cells

Viruses
Mark K LaffertyAlfredo Garzino-Demo

Abstract

Chemokine 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-3α 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 progress...Continue Reading

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Citations

Jan 19, 2018·Journal of Leukocyte Biology·Daniela Angela CovinoLaura Fantuzzi
Aug 7, 2019·Current Medicinal Chemistry·David C Brice, Gill Diamond
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Jun 25, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Anna Lucia TorneselloMaria Lina Tornesello

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Methods Mentioned

BETA
deamination
flow cytometry
enzyme-linked
Protein
electrophoresis
gel filtration
Gel
Immunoprecipitation
PCR
ChIP

Software Mentioned

GraphPad Prism
GraphPad
FlowJo

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