title: HIV-1 Envelope Mimicry of Host Enzyme Kynureninase Does Not Disrupt Tryptophan Metabolism.
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 VHDJHand VLJLknock-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.
authors.affiliation: Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710; todd.bradley@duke.edu garnett.kelsoe@dm.duke.edu barton.haynes@dm.duke.edu.|Department of Medicine, Duke University Medical Center, Durham, NC 27710.
authors.forename: Todd
authors.initials: T
authors.lastname: Bradley
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC 27710.
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.affiliation: Department of Pathology, Duke University Medical Center, Durham, NC 27710.
authors.forename: Olga
authors.initials: O
authors.lastname: Ilkayeva
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC 27710.
authors.forename: T Matt
authors.initials: TM
authors.lastname: Holl
authors.affiliation: Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710.
authors.forename: Ruijun
authors.identifier: 0000-0002-2342-8232
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710.
authors.forename: Jinsong
authors.identifier: 0000-0002-2195-2997
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215.
authors.forename: Sampa
authors.identifier: 0000-0002-8796-1714
authors.initials: S
authors.lastname: Santra
authors.affiliation: Infectious Disease Research Institute, Seattle, WA 98102.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Fox
authors.affiliation: Infectious Disease Research Institute, Seattle, WA 98102.
authors.forename: Steve G
authors.initials: SG
authors.lastname: Reed
authors.affiliation: Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710.
authors.forename: Robert
authors.initials: R
authors.lastname: Parks
authors.affiliation: Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710.
authors.forename: Cindy M
authors.identifier: 0000-0002-6903-2831
authors.initials: CM
authors.lastname: Bowman
authors.affiliation: Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710.
authors.forename: Hilary
authors.initials: H
authors.lastname: Bouton-Verville
authors.affiliation: Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710.
authors.forename: Laura L
authors.initials: LL
authors.lastname: Sutherland
authors.affiliation: Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Scearce
authors.affiliation: Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710.|Department of Medicine, Duke University Medical Center, Durham, NC 27710.
authors.forename: Nathan
authors.initials: N
authors.lastname: Vandergrift
authors.affiliation: Department of Microbiology, Boston University, Boston, MA 02215.
authors.forename: Thomas B
authors.identifier: 0000-0002-1383-6865
authors.initials: TB
authors.lastname: Kepler
authors.affiliation: Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710.|Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710.
authors.forename: M Anthony
authors.identifier: 0000-0002-3890-5855
authors.initials: MA
authors.lastname: Moody
authors.affiliation: Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710.
authors.forename: Hua-Xin
authors.initials: HX
authors.lastname: Liao
authors.affiliation: Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710.|Department of Medicine, Duke University Medical Center, Durham, NC 27710.
authors.forename: S Munir
authors.initials: SM
authors.lastname: Alam
authors.affiliation: Department of Pathology, Duke University Medical Center, Durham, NC 27710.
authors.forename: Roger
authors.identifier: 0000-0001-6682-4588
authors.initials: R
authors.lastname: McLendon
authors.affiliation: Department of Pathology, Duke University Medical Center, Durham, NC 27710.
authors.forename: Jeffrey I
authors.identifier: 0000-0003-0273-6284
authors.initials: JI
authors.lastname: Everitt
authors.affiliation: Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Newgard
authors.affiliation: Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710.|Department of Medicine, Duke University Medical Center, Durham, NC 27710.|Department of Pathology, Duke University Medical Center, Durham, NC 27710.
authors.forename: Laurent
authors.identifier: 0000-0001-7497-6645
authors.initials: L
authors.lastname: Verkoczy
authors.affiliation: Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710; todd.bradley@duke.edu garnett.kelsoe@dm.duke.edu barton.haynes@dm.duke.edu.|Department of Immunology, Duke University Medical Center, Durham, NC 27710.
authors.forename: Garnett
authors.initials: G
authors.lastname: Kelsoe
authors.affiliation: Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710; todd.bradley@duke.edu garnett.kelsoe@dm.duke.edu barton.haynes@dm.duke.edu.|Department of Medicine, Duke University Medical Center, Durham, NC 27710.|Department of Pathology, Duke University Medical Center, Durham, NC 27710.
authors.forename: Barton F
authors.initials: BF
authors.lastname: Haynes
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000378:metabolism; D003429:Cross Reactions; D015483:HIV Antibodies / Q000378:metabolism; D015700:HIV Envelope Protein gp41 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D054884:Host-Pathogen Interactions; D006801:Humans; D006867:Hydrolases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D057131:Immune Evasion; D008253:Macaca mulatta; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018716:Molecular Mimicry; D010455:Peptides / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014364:Tryptophan / Q000378:metabolism*; D014611:Vaccination; D022223:Vaccines, Subunit
chemical_list: D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D015700:HIV Envelope Protein gp41; D010455:Peptides; D022223:Vaccines, Subunit; D014364:Tryptophan; D006867:Hydrolases; C021480:kynureninase