Int Conf AIDS 2000 Jul 9-14; 13:(abstract no. WeOrA593)
O'Connor D, Evans D, Mothe B, Allen T, Dzuris J, Sette A, Watkins D D. O'Connor, Wisconsin Regional Primate Research Center, 1220 Capitol Court, Madison, WI, 53715, United States, Tel.: +1 608 265 3379, Fax: +1 608 262 5494, E-mail: doconnor@primate.wisc.edu
Natural selection for high-fitness human immunodeficiency virus (HIV) variants occurs during the course of infection. Selection for altered host cell tropism, decreased susceptibility to neutralizing antibodies, and broadened coreceptor usage has been thoroughly documented. While these examples of selection are important for understanding viral pathogenesis, they do not establish causative links among the evolution of quasispecies, the development of particular host immune responses, and disease progression. Recent studies in our lab have searched for this type of correlation by studying viral escape from the cytotoxic T lymphocyte (CTL) response. CTL epitopes are typically 9-11 amino acids in length and are determined by the complement of major histocompatibility complex class I (MHC-I) alleles expressed by an individual. Therefore, discreet and unique regions of the virus are recognized in each infection. This contrasts to selection on antibody epitopes and cell tropism that occurs within the same well-defined viral regions in all infected individuals. By defining animals' MHC class I loci and mapping new CTL epitopes, we have analyzed the coevolution of the CTL response and the virus in the course of simian immunodeficiency virus infection. To date, amino acid replacements have been found within each of 14 CTL epitopes. We have shown that selection for variant epitopes occurs within Gag, Pol, Env, Rev, Tat, and Nef CTL epitopes. Furthermore, we have shown that these variant epitopes fail to sensitize target cells for lysis and/or reduce binding to class I molecules. This work has provided unequivocal evidence for viral escape from CTL. The apparent escape from all epitopes recognized by an animal's CTL suggests an important role for CTL in containing the virus during chronic infection.
Keywords: AEGIS, SIV, Epitopes, T-Lymphocytes, Cytotoxic, HIV, HIV Infections, HIV Envelope Protein gp41, HIV Envelope Protein gp120, Disease Progression, HIV Antigens, Human, immunology 000709
WeOrA593
