Early modifications of host cell gene expression induced by HIV-1

Objective: Characterization of the effects of infection with HIV-1 on cellular gene expression. Design and methods: Differential RNA display was applied to compare uninfected and HIV-1(LAI)-infected CEM cells 24 h post-inoculation. Differential bands were selected, cloned and several clones per band were sequenced. RNase protection assay was used to confirm differential display findings in HIV-1(LAI)-infected CEM cells as well as in another T-cell line (H9) infected with a different strain (HIV-1(SF33)). Results: Twelve differentially expressed bands, six up-and six downregulated in HIV-infected cells compared with controls, were selected. Four of the six upregulated bands were HIV transcripts. RNase protection assay of the remaining eight bands confirmed differential expression of four genes, including induction of a mariner transposase and moesin as well as suppression of alpha-nascent polypeptide-associated complex and mitochondrial heat shock protein 75 in HIV-1-infected cell cultures. Furthermore, a significant increase of glioma pathogenesis-related protein was found by RNase protection assay. Conclusions: Based on this initial limited differential display analysis, it was estimated that expression of 3% of the host genes was altered by HIV-1. Amongst the identified gene modifications, the induction of a mariner transposase may alter cellular gene expression itself, whilst the enhanced expression of glioma pathogenesis-related protein suggests a role in the host cell response to viral infection. The increase in moesin may facilitate viral budding and uptake. Furthermore, the suppression of alpha-nascent polypeptide-associated complex may promote translocation of HIV-1 polypeptides into the endoplasmic reticulum, whereas the downregulation of mitochondrial heat shock protein 75 may contribute to a cytopathic effect on mitochondria and possibly impairs antigen presentation. (C) 1998 Lippincott-Raven Publishers.