HTLV-1 Disrupts Cellular Histone Protein Levels

Cancer researchers have described a possible method used by the human T-lymphotropic virus type-1 (HTLV-1) to destabilize the T-cell's genetic machinery and possibly start the cell on the road to leukemia or lymphoma.

Investigators at Colorado State University (Fort Collins, USA) worked with T-cell cultures, which they either infected with HTLV-1 or treated with an isolated HTLV-1 protein called Tax. Tax was known to promote inappropriate cellular proliferation, repress multiple DNA repair mechanisms, deregulate cell cycle checkpoints, and induce genomic instability.

Results published in the January 31, 2008, online edition of the journal Retrovirolgy revealed that histone protein levels were reduced in HTLV-1 infected T-cell lines (HuT102, SLB-1, and C81) relative to uninfected T-cell lines (CEM, Jurkat, and Molt4), while the relative amount of DNA per haploid complement was unaffected. HTLV-1 infection uncoupled replication-dependent histone gene expression and DNA replication, allowing the depletion of histone proteins with cell division. A similar effect was seen in the Jurkat cells after treatment with Tax.

The investigators summarized their results by writing that, "we suggest Tax repression of replication-dependent histone gene expression will result in reactivation of viral gene expression, deregulation of cellular gene expression, and genomic instability. All of these effects may contribute to the development of adult T-cell leukemia/lymphoma. To our knowledge, this is the first example of a reduction of histone levels correlating with viral infection and cancer development.”


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