Evolutionary Stable Strategy: A Test for Theories of Retroviral Pathology which are Based upon the Concept of Molecular Mimicry

• Published in: Journal of theoretical biology 2000-02, Vol.202 (3), p.213-229
• Main Authors: POWELL, P.D., DEMARTINI, J.C., AZARI, P., STARGELL, L.A., CORDAIN, L., TUCKER, A.
• Format: Article
• Language: English
• Subjects: Acquired Immunodeficiency Syndrome - genetics; Acquired Immunodeficiency Syndrome - immunology; Acquired Immunodeficiency Syndrome - virology; Animals; Ape Diseases - genetics; Ape Diseases - immunology; Ape Diseases - virology; Genes, MHC Class II - genetics; HIV-1 - genetics; HIV-1 - immunology; Human immunodeficiency virus 1; Humans; Immune System - immunology; Immune System - virology; molecular mimicry; Molecular Mimicry - genetics; Polymorphism, Genetic; quasispecies; Sequence Homology; transmembrane proteins
• ISSN: 0022-5193; 1095-8541
• DOI: 10.1006/jtbi.1999.1055

The genetic makeup of animal and plant populations is determined by established principles and concepts. Ecology and evolution provide a basic theoretical framework for understanding how genetic changes occur in populations. Whether these rules can be applied to host retroviral populations is unknown. Individuals infected with the human immunodeficiency virus (HIV) contain within their bodies a viral population. This population is known as a viral quasispecies. Located in the transmembrane protein of HIV-1 is the viral sequence Gly-Thr-Asp-Arg-Val. Previous immunological studies have shown that viral antibody is produced in response to this five-amino-acid sequence. Antibody to this viral sequence also crossreacts and binds to a related peptide sequence found on certain immune cells. This related sequence, Gly-Thr-Glu-Arg-Val, is found on immune cells bearing a structure known as the major histocompatibility complex (MHC). The viral transmembrane sequence, Gly-Thr-Asp-Arg-Val, can be substituted with alanine residues utilizing site-directed mutagenesis. This creates a viral clone devoid of the genetic similarity with the MHC. Chimpanzees progressing to AIDS contain both sequences of interest. Suppression of the chimpanzee quasispecies utilizing anti-retroviral drugs is proposed. This action serves to suppress the presence of the viruses containing the sequence Gly-Thr-Asp-Arg-Val. When viral load has been reduced significantly, a drug resistant, alanine altered clone is to be introduced in large numbers. The concept of evolutionary stable strategy predicts that a viable HIV clone with alanine residues can genetically dominate the viral population. Immune system recognition of the alanine sequence is likely to result in renewed antibody production. Antibodies to the alanine containing viral sequence should not recognize or bind to the MHC. Immunological parameters can then be measured to determine the physiological impact of eliminating a sequence responsible for molecular mimicry between virus and host.