Human Chromosome 12 Is Required for Elevated HIV-1 Expression in Human-Hamster Hybrid Cells

Abstract

Host cell factors act together with regulatory genes of the human immunodeficiency virus (HIV) to control virus production. Human-Chinese hamster ovary hybrid cell clones were used to probe for human chromosomes involved in regulating HIV gene expression. DNA transfection experiments showed that 4 of 18 clones had high levels of HIV gene expression measured by both extracellular virus production and transactivation of the HIV long terminal repeat in the presence of the trans-activator (tat) gene. Karyotype analyses revealed a 94% concordance (17/18) between human chromosome 12 and HIV gene expression. Other chromosomes had an 11 to 72% concordance with virus production.

Lentiviral vectors: turning a deadly foe into a therapeutic agent

“…The stereotactic injection of only a few microliters of vector preparation allows the transduction of tens to hundreds of thousands of neurons in the absence of any significant inflammatory or vectorspecific immune response. [11][12][13][14][15][16][17][18][19][20][21][22][23][24] The expression of the foreign protein is long-lasting, at least for the transgenes that have been tested so far. While VSV G-pseudotyped particles target neurons almost exclusively, preliminary evidence indicates that other viral envelopes might permit the more efficient transduction of cells such as astrocytes.…”

“…This issue remains to be probed, but several species-specific restrictions have been discovered in the biology of lentiviruses. [19][20][21][22][23] Second, the genGene Therapy omic complexity of HIV is far greater than that of most other lentiviruses, including feline immunodeficiency virus and equine infectious anemia virus, which each have only six genes instead of the nine present in their human counterpart. Because in all cases a minimum of three genes, gag, pol and rev, will likely be required to generate vector particles efficiently, the multiply attenuated HIV-based packaging system will be the farthest removed from its parental virus.…”

The Human Immunodeficiency Virus Transactivator Tat Interacts with the RNA Polymerase II Holoenzyme

“…However, cellular proteins clearly play a critical role in the function of Tat. At least one of these proteins is encoded on human chromosome 12 (hp12) and is required to tether Tat to TAR (1,2,(18)(19)(20). In addition, squelching experiments suggest the existence of other coactivators which mediate interactions between Tat and the cellular transcriptional machinery (6,35).…”

Cyclin T: Three forms for different roles in physiological and pathological functions

“…However, in rodent-human somatic cell hybrids and in rodent cells, which additionally contain human chromosome 12 (MHC915 and CHO12), levels of Tat transactivation approach those observed in human cells (Hart et al, 1989;Newstein et al, 1990). These findings suggested the existence of a cellular Tat cofactor encoded on human chromosome 12 (namely cyclin T1), which can bind to the central loop in TAR (Hart et al, 1995).…”