A reduction in histone protein levels is linked to T-lymphotropic virus type-1 (HTLV-1) infection and the development of cancer, according to Colorado State University investigators. HTLV-1 is a retrovirus that causes adult T-cell leukemia/lymphoma (ATLL).
A single protein made by the virus, Tax, is reportedly thought to be enough to trigger cancer development. Tax has a number of effects in the cell, including promoting inappropriate cell division, repressing DNA repair mechanisms, and causing genomic instability.
The investigators discovered that the levels of histone proteins and histone transcripts were lower in T-cell lines infected with HTLV-1 than in uninfected cell lines. They also showed that Tax could cause a drop in the levels of histone transcript in uninfected cells.
Histone proteins are required for the packaging of DNA in cell nuclei and are associated with DNA transcription, repair, and replication. “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,” the authors note. “All of these effects may contribute to the development of adult T-cell leukemia/lymphoma.”
The findings are published online in Retrovirology.