HIV-1 Envelope Mimicry of Host Enzyme Kynureninase Does Not Disrupt Tryptophan Metabolism.
J Immunol
; 197(12): 4663-4673, 2016 12 15.
Article
en En
| MEDLINE
| ID: mdl-27849170
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.
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Base de datos:
MEDLINE
Asunto principal:
Péptidos
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Triptófano
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Proteína gp41 de Envoltorio del VIH
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Infecciones por VIH
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VIH-1
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Vacunas contra el SIDA
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Hidrolasas
Idioma:
En
Revista:
J Immunol
Año:
2016
Tipo del documento:
Article