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J Immunol. 2016 Dec 15;197(12):4663-4673. Epub 2016 Nov 14.

HIV-1 Envelope Mimicry of Host Enzyme Kynureninase Does Not Disrupt Tryptophan Metabolism.

Author information

1
Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710; todd.bradley@duke.edu garnett.kelsoe@dm.duke.edu barton.haynes@dm.duke.edu.
2
Department of Medicine, Duke University Medical Center, Durham, NC 27710.
3
Department of Immunology, Duke University Medical Center, Durham, NC 27710.
4
Department of Pathology, Duke University Medical Center, Durham, NC 27710.
5
Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710.
6
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215.
7
Infectious Disease Research Institute, Seattle, WA 98102.
8
Department of Microbiology, Boston University, Boston, MA 02215.
9
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710.

Abstract

The HIV-1 envelope protein (Env) has evolved to subvert the host immune system, hindering viral control by the host. The tryptophan metabolic enzyme kynureninase (KYNU) is mimicked by a portion of the HIV Env gp41 membrane proximal region (MPER) and is cross-reactive with the HIV broadly neutralizing Ab (bnAb) 2F5. Molecular mimicry of host proteins by pathogens can lead to autoimmune disease. In this article, we demonstrate that neither the 2F5 bnAb nor HIV MPER-KYNU cross-reactive Abs elicited by immunization with an MPER peptide-liposome vaccine in 2F5 bnAb VHDJH and VLJL knock-in mice and rhesus macaques modified KYNU activity or disrupted tissue tryptophan metabolism. Thus, molecular mimicry by HIV-1 Env that promotes the evasion of host anti-HIV-1 Ab responses can be directed toward nonfunctional host protein epitopes that do not impair host protein function. Therefore, the 2F5 HIV Env gp41 region is a key and safe target for HIV-1 vaccine development.

PMID:
27849170
PMCID:
PMC5136304
DOI:
10.4049/jimmunol.1601484
[Indexed for MEDLINE]
Free PMC Article

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