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Contribution of CD8+ T cells to containment of viral replication and emergence of mutations in Mamu-A*01-restricted epitopes in Simian immunodeficiency virus-infected rhesus monkeys
Authors:Kim Eun-Young  Veazey Ronald S  Zahn Roland  McEvers Kimberly J  Baumeister Susanne H C  Foster Gabriel J  Rett Melisa D  Newberg Michael H  Kuroda Marcelo J  Rieber E Peter  Piatak Michael  Lifson Jeffrey D  Letvin Norman L  Wolinsky Steven M  Schmitz Jörn E
Institution:Division of Infectious Diseases, The Feinberg School of Medicine, Northwestern University, 676 N. St. Clair St., Suite 200, Chicago, IL 60611, USA. e-kim@northwestern.edu
Abstract:Here, we investigated the containment of virus replication in simian immunodeficiency virus (SIV) infection by CD8(+) lymphocytes. Escape mutations in Mamu-A*01 epitopes appeared first in SIV Tat TL8 and then in SIV Gag p11C. The appearance of escape mutations in SIV Gag p11C was coincident with compensatory changes outside of the epitope. Eliminating CD8(+) lymphocytes from rhesus monkeys during primary infection resulted in more rapid disease progression that was associated with preservation of canonical epitopes. These results confirm the importance of cytotoxic T cells in controlling viremia and the constraint on epitope sequences that require compensatory changes to go to fixation.
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