An "Escape Clock'' for Estimating the Turnover of SIV DNA in Resting CD4+T Cells
AuthorReece, J; Petravic, J; Balamurali, M; Loh, L; Gooneratne, S; De Rose, R; Kent, SJ; Davenport, MP
Source TitlePLoS Pathogens
PublisherPUBLIC LIBRARY SCIENCE
University of Melbourne Author/sREECE, JEANETTE; Loh, Liyen; Gooneratne, Dona; De Rose, Robert; Kent, Stephen; Reece, Jeanette
AffiliationMicrobiology and Immunology
Chemical and Biomolecular Engineering
Medicine and Radiology
Melbourne School of Population and Global Health
Document TypeJournal Article
CitationsReece, J., Petravic, J., Balamurali, M., Loh, L., Gooneratne, S., De Rose, R., Kent, S. J. & Davenport, M. P. (2012). An "Escape Clock'' for Estimating the Turnover of SIV DNA in Resting CD4+T Cells. PLOS PATHOGENS, 8 (4), https://doi.org/10.1371/journal.ppat.1002615.
Access StatusOpen Access
Persistence of HIV DNA presents a major barrier to the complete control of HIV infection under current therapies. Most studies suggest that cells with latently integrated HIV decay very slowly under therapy. However, it is much more difficult to study the turnover and persistence of HIV DNA during active infection. We have developed an "escape clock" approach for measuring the turnover of HIV DNA in resting CD4+ T cells. This approach studies the replacement of wild-type (WT) SIV DNA present in early infection by CTL escape mutant (EM) strains during later infection. Using a strain-specific real time PCR assay, we quantified the relative amounts of WT and EM strains in plasma SIV RNA and cellular SIV DNA. Thus we can track the formation and turnover of SIV DNA in sorted resting CD4+ T cells. We studied serial plasma and PBMC samples from 20 SIV-infected Mane-A*10 positive pigtail macaques that have a signature Gag CTL escape mutation. In animals with low viral load, WT virus laid down early in infection is extremely stable, and the decay of this WT species is very slow, consistent with findings in subjects on anti-retroviral medications. However, during active, high level infection, most SIV DNA in resting cells was turning over rapidly, suggesting a large pool of short-lived DNA produced by recent infection events. Our results suggest that, in order to reduce the formation of a stable population of SIV DNA, it will be important either to intervene very early or intervene during active replication.
- Click on "Export Reference in RIS Format" and choose "open with... Endnote".
- Click on "Export Reference in RIS Format". Login to Refworks, go to References => Import References