Evolutionary stable strategy: A test for theories of retroviral pathology which are based upon the concept of molecular mimicry

The genetic makeup of animal and plant populations is determined by establi shed principles and concepts. Ecology and evolution provide a basic theoret ical framework for understanding how genetic changes occur in populations. Whether these rules can be applied to host retroviral populations is unknow n. Individuals infected with the human immunodeficiency virus (HIV) contain within their bodies a viral population. This population is known as a vira l quasispecies. Located in the transmembrane protein of HIV-1 is the viral sequence Gly-Thr-Asp-Arg-Val. Previous immunological studies have shown tha t viral antibody is produced in response to this five-amino-acid sequence. Antibody to this viral sequence also crossreacts and binds to a related pep tide 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 maj or histocompatibility complex (MHC). The viral transmembrane sequence, Gly- Thr-Asp-Arg-Val, can be substituted with alanine residues utilizing site-di rected mutagenesis. This creates a viral clone devoid of the genetic simila rity with the MHC. Chimpanzees progressing to AIDS contain both sequences o f interest. Suppression of the chimpanzee quasispecies utilizing anti-retro viral 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 b een reduced significantly, a drug resistant, alanine altered clone is to be introduced in large numbers. The concept of evolutionary stable strategy p redicts that a viable HIV clone with alanine residues can genetically domin ate the viral population. Immune system recognition of the alanine sequence is likely to result in renewed antibody production. Antibodies to the alan ine containing viral sequence should not recognize or bind to the MHC. Immu nological parameters can then be measured to determine the physiological im pact of eliminating a sequence responsible for molecular mimicry between vi rus and host. (C) 2000 Academic Press.