[Frontiers in Bioscience E3, 1385-1400, June 1, 2011]

Charting the peptide crossreactome between HIV-1 and the human proteome

Guglielmo Lucchese1, Angela Stufano1, Michele Calabro1, Darja Kanduc1

1Department of Biochemistry and Molecular Biology,Ernesto Quagliariello, University of Bari, Bari, Italy

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Methods
4. Results 4.1. Theoretical and empirical values of the viral versus human heptapeptide overlap
4.2. Quantifying the immune cross-reactivity risk between HIV-1 and human proteins
4.3. Analyzing the pathologies potentially associated to HIV-1 cross-reactivity
4.3.1. HIV-1 heptapeptide cross-reactivity and immunosuppression.
4.3.2. HIV-1 heptapeptide cross-reactivity and neurological disorders.
4.3.3. HIV-1 heptapeptide cross-reactivity and muscle diseases.
4.3.4. HIV-1 heptapeptide cross-reactivity and malignancies.
4.3.5. HIV-1 cross-reactivity and other AIDS disorders: lipodystrophies, diarrhea, bone loss, corneal alterations, kidney disease, hypertension.
4.4. Analyzing sequence similarity of HIV-1 polyprotein to the human proteome at the pentapeptide level.
5. Discussion
6. Contributions
7. References

1. ABSTRACT

This paper defines potential peptide cross-reactivity between HIV-1 and the human host. Specifically, the amino acid primary sequence of HIV-1, isolate CDC-451, was analyzed for potential immunopathological relationships with the human proteome. The results revealed that: 1) HIV-1 shares 50 heptapeptides and three octapeptides with the human proteome; 2) 34 of the 50 shared heptapeptides are experimentally validated epitopes targeted by immune responses following HIV-1 infection; 3) the viral heptapeptide epitopes are present in human proteins that, when altered, are associated with disease characteristics of acquired immunodeficiency syndrome (AIDS) such as CD4+ cell loss, encephalopathy, schizophrenia, myopathy, cardiovascular disorders, hypertension, corneal diseases, diarrhea, lymphoma, and bladder cancer; 4) at the pentapeptide level, the viral-versus-human overlap is extensive (14,227 matches), with the viral pentapeptides disseminated throughout 10,312 human proteins. The findings are discussed in relationship to HIV-1 escape from immune surveillance, adjuvant-induced HIV-1 immunogenicity, autoimmune cross-reactions following human hyperimmune responses against HIV-1, and AIDS.