Expansion and Exhaustion of T-cell Responses During Mutational Escape from Long-term Viral Control in Two DNA/modified Vaccinia Virus Ankara-vaccinated and Simian-human Immunodeficiency Virus SHIV-89.6P-challenged Macaques

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 2008 Feb 1

PMID 18234787

Citations 8

Authors

Shanmugalakshmi Sadagopal

Rama Rao Amara

Sunil Kannanganat

Sunita Sharma

Lakshmi Chennareddi

Harriet L Robinson

Affiliations

Soon will be listed here.

Abstract

In this study, we monitored the temporal breadths, frequencies, and functions of antiviral CD4 and CD8 T cells in 2 of 22 DNA/modified vaccinia virus Ankara-vaccinated macaques that lost control of a simian-human immunodeficiency virus 89.6P challenge by 196 weeks postchallenge. Our results show that both mutation and exhaustion contributed to escape. With the reappearance of viremia, responding CD8 and CD4 T cells underwent an initial increase and then loss of breadth and frequency. Antiviral gamma interferon (IFN-gamma)- and interleukin 2-coproducing cells were lost before IFN-gamma-producing cells and CD4 cells before CD8 cells. At euthanasia, all CD8, but no CD4, Gag epitopes detected during long-term control contained mutations.

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