T cells contain an RNase-insensitive inhibitor of APOBEC3G deaminase activity

Beth K. Thielen, Kevin C. Klein, Lorne W. Walker, Mary Rieck, Jane H. Buckner, Garrett W. Tomblingson, Jaisri R. Lingappa

Research output: Contribution to journalArticlepeer-review

36 Scopus citations


The deoxycytidine deaminase APOBEC3G (A3G) is expressed in human T cells and inhibits HIV-1 replication. When transfected into A3G-deficient epithelial cell lines, A3G induces catastrophic hypermutation by deaminating the HIV-1 genome. Interestingly, studies suggest that endogenous A3G in T cells induces less hypermutation than would be expected. However, to date, the specific deaminase activity of endogenous A3G in human CD4+ T cells has not been examined directly. Here, we compared deaminase activity of endogenous and exogenous A3G in various human cell lines using a standard assay and a novel, quantitative, high-throughput assay. Exogenous A3G in epithelial cell lysates displayed deaminase activity only following RNase treatment, as expected given that A3G is known to form an enzymatically inactive RNA-containing complex. Surprisingly, comparable amounts of endogenous A3G from T cell lines or from resting or activated primary CD4+T cells exhibited minimal deaminase activity, despite RNase treatment. Specific deaminase activity of endogenous A3G in H9, CEM, and other T cell lines was up to 36-fold lower than specific activity of exogenous A3G in epithelial-derived cell lines. Furthermore, RNase-treated T cell lysates conferred a dose-dependent inhibition to epithelial cell lysates expressing enzymatically active A3G. These studies suggest that T cells, unlike epithelial-derived cell lines, express an unidentified RNase-resistant factor that inhibits A3G deaminase activity. This factor could be responsible for reduced levels of hypermutation in T cells, and its identification and blockade could offer a means for increasing antiretroviral intrinsic immunity of T cells.

Original languageEnglish (US)
Pages (from-to)1320-1334
Number of pages15
JournalPLoS pathogens
Issue number9
StatePublished - Sep 2007
Externally publishedYes


Dive into the research topics of 'T cells contain an RNase-insensitive inhibitor of APOBEC3G deaminase activity'. Together they form a unique fingerprint.

Cite this