complexity of the inoculum determines the rate of reversion of siv gag cd8 t cell mutant virus and outcome of infection培养液的复杂性决定了siv插科打诨的降级率cd8 t细胞突变病毒和感染的结果.pdf

Complexity of the Inoculum Determines the Rate of Reversion of SIV Gag CD8 T Cell Mutant Virus and Outcome of Infection 1 1 1 1 1 Liyen Loh , Jeanette C. Reece , Caroline S. Fernandez , Sheilajen Alcantara , Robert Center , Jane 1 1 2 2 2 Howard , Damian F. J. Purcell , Mehala Balamurali , Janka Petravic , Miles P. Davenport , Stephen J. Kent1* 1 Department of Microbiology and Immunology, University of Melbourne, Melbourne, Victoria, Australia, 2 Center for Vascular Research, University of New South Wales, Sydney, Australia Abstract Escape mutant (EM) virus that evades CD8+ T cell recognition is frequently observed following infection with HIV-1 or SIV. This EM virus is often less replicatively ‘‘fit’’ compared to wild-type (WT) virus, as demonstrated by reversion to WT upon ¨ transmission of HIV to a naıve host and the association of EM virus with lower viral load in vivo in HIV-1 infection. The rate and timing of reversion is, however, highly variable. We quantified reversion to WT of a series of SIV and SHIV viruses containing minor amounts of WT virus in pigtail macaques using a sensitive PCR assay. Infection with mixes of EM and WT virus containing $10% WT virus results in immediate and rapid outgrowth of WT virus at SIV Gag CD8 T cell epitopes within 7 days of infection of pigtail macaques with SHIV or SIV. In contrast, infection with biologically passaged SHIVmn229 viruses with much smaller proportions of WT sequence, or a molecular clone of pure EM SIVmac239, demonstrated a delayed or slow pattern of reversion. WT virus wa