Reversal of proviral latency is being pursued as a curative strategy for HIV-1 infection. Recent clinical studies of in vivo administration of the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA; vorinostat) show increases in unspliced cellular HIV-1 RNA levels in resting CD4(+) T cells. A critical unknown, however, is the proportion of latent proviruses that can be transcri...

The persistence of latent, replication-competent HIV-1 proviruses in resting CD4+ T cells, and other cellular reservoirs, represents a major barrier to cure. This reservoir is impervious the immune system antiretroviral therapy, but has potential produce infectious rebound virus if therapy interrupted. There are multiple ongoing efforts identify and/or develop novel therapeutic strategies elimi...

The DNA from 17 lymphoid tumors induced by bovine leukemia virus (BLV) was digested with the restriction endonuclease EcoRI. Filter hybridization analysis using radioactive probes specific for the BLV genome showed that all tumors contained at least one or a portion of one provirus. Digestion of these proviruses with Sac I demonstrated that deletions occurred in about 25% of the cases and invol...

The HIV-1 Vif protein is essential for overcoming the antiviral activity of DNA-editing apolipoprotein B mRNA editing enzyme, catalytic polypeptide 3 (APOBEC3) cytidine deaminases. We show that naturally occurring HIV-1 Vif point mutants with suboptimal anti-APOBEC3G activity induce the appearance of proviruses with lamivudine (3TC) drug resistance-associated mutations before any drug exposure....

Restriction analysis of the approximately 100 integrated baboon endogenous virus (BaEV) proviruses in baboon cells and tissues has revealed two major sequence variations, both in the gag gene region of the genome. One, a 150 nucleotide pair insert, is present in a small proportion of the proviral DNAs and some baboons, but is present in the majority of the proviral DNAs of other baboons. The se...

Clonal expansion of infected CD4+ T cells is a major mechanism HIV-1 persistence and barrier to achieving cure. Potential causes are homeostatic proliferation, effects integration, interaction with antigens. Here, we show that it possible link antigen responsiveness, the full proviral sequence, integration site, cell receptor β-chain (TCRβ) sequence examine role recurrent antigenic exposure in ...

The expression of the v-rel oncogene of avian reticuloendotheliosis virus (REV-T) transforms and immortalizes very immature avian lymphoid cells. In REV-T-transformed lymphoid cells which were persistently infected with reticuloendotheliosis-associated virus (REV-A), the REV-T proviral copy number increases after the initial integration event. In 23 independently derived REV-T-transformed cell ...

Proviral copies of mouse mammary tumor virus (MMTV) are known to be amplified in certain T-cell lymphomas. Transcription of the amplified MMTV proviruses was studied in detail in two T-cell lymphoma lines and showed the production of deletions and premature termination of env mRNAs and the premature termination of gag transcripts. EL-4 cells produce three env mRNAs, and sequence analysis of cDN...

The human endogenous retrovirus K family (HERV-K) comprises 30 to 50 closely related proviruses, most of which are defective. In contrast to all other human endogenous retroviruses, some HERV-K proviruses have maintained open reading frames for all viral proteins. In addition to the structural proteins Gag and Env and the reverse transcriptase, two regulatory proteins (Rec and Np9) have been de...

Highly active antiretroviral therapy (HAART) can reduce human immunodeficiency virus type 1 (HIV-1) viremia to clinically undetectable levels. Despite this dramatic reduction, some virus is present in the blood. In addition, a long-lived latent reservoir for HIV-1 exists in resting memory CD4(+) T cells. This reservoir is believed to be a source of the residual viremia and is the focus of eradi...