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

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.

Duke Scholars

Author Michael Anthony Moody Pediatrics, Infectious Diseases

Author Olga Ilkayeva Medicine, Endocrinology, Metabolism, and Nutrition

Author S. Munir Alam Medicine, Duke Human Vaccine Institute

Author Roger Edwin McLendon Pathology

Author Jeffrey Ira Everitt Pathology

Author Christopher Bang Newgard Pharmacology & Cancer Biology

Author Garnett H. Kelsoe Integrative Immunobiology

Author Barton Ford Haynes Medicine, Duke Human Vaccine Institute