Human Beta Defensin 2 Selectively Inhibits HIV-1 in Highly Permissive CCR6 CD4 T CellsReportar como inadecuado


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


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1

Division of Basic Science, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA

2

Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA

3

Department of Biochemistry, University of Maryland School of Medicine, Baltimore, MD 21201, USA

4

Department of Molecular Medicine, University of Padova, Padova 35121, Italy





*

Author to whom correspondence should be addressed.



Academic Editor: Theresa Chang

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 progression. View Full-Text

Keywords: defensins; viruses; immune response; HIV; CCR6; pathogenesis; human beta defensin 2; Th17 defensins; viruses; immune response; HIV; CCR6; pathogenesis; human beta defensin 2; Th17





Autor: Mark K. Lafferty 1,2, Lingling Sun 1, Aaron Christensen-Quick 1,2, Wuyuan Lu 1,3 and Alfredo Garzino-Demo 1,2,4,*

Fuente: http://mdpi.com/



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