Human polyomavirus 6 differentially infects healthy and tumor tissue in the colon: A case report

Human polyomavirus 6 (HPyV6) is part of the human skin virome. Like other HPyVs, it encodes proteins with oncogenic properties.

A 73-year-old Italian female patient with stage II right-sided colon adenocarcinoma underwent hemicolectomy; she died one month later because of bacterial sepsis. Colon tumor (T), adjacent healthy (AH) tissue, and serum samples were collected. Total nucleic acids were subjected to next-generation sequencing, followed by metagenomics analysis. HPyV detection was confirmed by real-time PCR and Rolling Circle Amplification (RCA); HPyV6 transcripts and proteins were identified by means of PCR and Western blot/mass spectrometry, respectively.

Viral metagenomics analysis revealed the presence of several viral genomes, mainly belonging to unclassified viruses and phages, in both AH and T tissues. HPyV6 DNA was detected in the T tissue, representing 7 % of the viral sequences, but not in the AH tissue. Subsequent molecular analysis confirmed the presence of the HPyV6 genomes (3.3x10⁶copies/ug) as episomes, infecting 19.8 % of the tumor cells; LT-Ag and VP1 transcripts were expressed in the T tissue, and the LT-Ag protein was expressed twice as highly in the T tissue as in the AH tissue.

This is the first report of the differential presence and expression of the HPyV6 genome in colon tumors but not in the AH tissue. These results are indicative of ongoing active replication of the virus, which might play a triggering role in malignant transformation.