APOBEC3G cytosine deamination hotspots are defined by both sequence context and single-stranded DNA secondary structure.

Apolipoprotein B mRNA-editing, enzyme-catalytic, polypeptide-like 3G (i.e., APOBEC3G or A3G) is an evolutionarily conserved cytosine deaminase that potently restricts human immunodeficiency virus type 1 (HIV-1), retrotransposons and other viruses.

Variation of HIV-1 mutation spectra among cell types.

The high rates of mutation, recombination, and replication drive HIV-1 diversity. In this study, we investigated how cell type affects viral mutation rate and mutation spectra. In studying four different cell types, no differences in mutation rate were observed, but intriguingly cell type differences impacted HIV-1 mutation spectra.

Concomitant lethal mutagenesis of human immunodeficiency virus type 1.

RNA virus population dynamics are complex, and sophisticated approaches are needed in many cases for therapeutic intervention. One such approach, termed lethal mutagenesis, is directed at targeting the virus population structure for extinction or error catastrophe. Previous studies have demonstrated the concept of this approach with human immunodeficiency virus type 1 (HIV-1) by use of chemical mutagens [i.

Activity of a novel combined antiretroviral therapy of gemcitabine and decitabine in a mouse model for HIV-1.

The emergence of drug resistance threatens to limit the use of current anti-HIV-1 drugs and highlights the need to expand the number of treatment options available for HIV-1-infected individuals. Our previous studies demonstrated that two clinically approved drugs, decitabine and gemcitabine, potently inhibited HIV-1 replication in cell culture through a mechanism that is distinct from the mechanisms for the drugs currently used to treat HIV-1 infection. We further demonstrated that gemcitabine inhibited replication of a related retrovirus, murine leukemia virus (MuLV), in vivo using the MuLV-based LP-BM5/murine AIDS (MAIDS) mouse model at doses that were not toxic.

Analysis of the ex vivo and in vivo antiretroviral activity of gemcitabine.

Replication of retroviral and host genomes requires ribonucleotide reductase to convert rNTPs to dNTPs, which are then used as substrates for DNA synthesis. Inhibition of ribonucleotide reductase by hydroxyurea (HU) has been previously used to treat cancers as well as HIV. However, the use of HU as an antiretroviral is limited by its associated toxicities such as myelosuppression and hepatotoxicity.