Molecular biology of human polyomaviruses

Division Of Basic Sciences - Nci

Investigators

Linked publications & trials

Abstract

We have developed bioinformatics approaches to discovering divergent new families of viruses in our deep sequencing datasets. The work led to the deposit of several thousand highly diverse previously virus species into public databases. In a parallel set of studies, we discovered several previously unrecognized families of animal viruses. We have suggested the names adomavirus, adintovirus, and ahomavirus. The names denote the distant relationships of the new families to known families, including adenoviruses, parvoviruses, and retroviruses. These lines of investigation are presently in press or under peer review. A related study involving the molecular biology of the virion proteins of a new group of arachnid-associated polyomaviruses we discovered promises to draw further evolutionary ties between multiple families of non-enveloped animal DNA viruses. We have been collaborating with NIH Clinical Center colleagues to investigate cases of human polyomavirus 7 (HPyV7) associated pruritic rashes. The project led to the discovery of a previously unknown HPyV7 protein that we dub "Agnoprotein." We are testing the hypothesis that Agnoprotein is involved in assembly of the HPyV7 and we are exploring the possibility that the protein directly triggers receptors involved in itch perception. A related project seeks to develop recombinant HPyV7-neutralizing monoclonal antibodies that could be used for treatment of HPyV7 pruritis. In collaboration with colleagues at NCI DCEG, we have performed deep sequencing of bladder cancers affecting organ transplant recipients, who are known to be at increased risk of developing bladder cancer. The work shows that bladder cancers from immunosuppressed individuals often harbor polyomaviruses or papillomaviruses. The results suggest a possible causal role for these viruses and raise the possibility that the vaccine we are developing against BK and JC polyomaviruses might prevent bladder cancer. In FY24 and FY25 we completed a broad survey of the NCBI Sequence Read Archive and deposited hundreds of new virus species into GenBank. A manuscript covering the work is under revision at eLife after favorable peer review. The final version of the paper will be posted at eLife once we have completed our development of a publicly searchable database that will be housed by the NCI Cancer Data Service.