CUGBP1 is required for IFNbeta-mediated induction of dominant-negative CEBPbeta and suppression of SIV replication in macrophages.

Productive HIV replication in the CNS occurs very early after infection, yet HIV-associated cognitive disorders do not typically manifest until the development of AIDS, suggesting that mechanisms exist in the CNS to control HIV replication and associated virus-induced pathological changes during the acute and asymptomatic stages of disease. Using an established SIV/macaque model of HIV dementia, we recently demonstrated that the mechanisms regulating virus replication in the brain at these stages involve the production of IFNbeta, which induces the truncated, dominant-negative isoform of C/EBPbeta, also referred to as LIP (liver-enriched transcriptional inhibitory protein). Alternative translation of C/EBPbeta mRNA and increased production of LIP can be mediated by CUGBP1 (CUG-repeat RNA-binding protein 1).

Mechanism for the establishment of transcriptional HIV latency in the brain in a simian immunodeficiency virus-macaque model.

Background: The brain is considered to be a reservoir of latent human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV). We examined the mechanism by which innate immune responses contribute to the establishment of this reservoir.

Methods: Gene-specific RNA and DNA were quantitated using real-time reverse-transcription polymerase chain reaction (RT-PCR).

Stochastic and genetic factors influence tissue-specific decline in ageing C. elegans.

The nematode Caenorhabditis elegans is an important model for studying the genetics of ageing, with over 50 life-extension mutations known so far. However, little is known about the pathobiology of ageing in this species, limiting attempts to connect genotype with senescent phenotype. Using ultrastructural analysis and visualization of specific cell types with green fluorescent protein, we examined cell integrity in different tissues as the animal ages.