Search PubMedSearch

PubMed · 1337752

BK virus.

Abstract

BK virus is a human polyoma virus that infects the renal epithelium and remains latent until immunosuppression triggers reactivation. After reactivation, BK virus can be detected in the urine by methods currently available in the clinical laboratory. Correlations can be made between BK viruria and the occurrence of both renal and hepatic pathologies. BK virus is emerging as a significant pathogen in transplant patients. Additionally, the presence of BK virus DNA in primary brain and pancreatic tumors suggests that it may have oncogenic potential. Thus far, attempts to treat BK virus infection have been ineffective, though research has opened new avenues for treatment possibilities. Prevention of BK virus and other latent viral reactivation remains a challenge to viral research.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

D A Holt, J T Sinnott, R L Oehler, E A Bradley. 1992. BK virus.. https://doi.org/10.1086/648347

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

A BK virus episomal vector for constitutive high expression of exogenous cDNAs in human cells.

A BK virus (BKV) episomal vector (pRPneoCMV) was constructed for expression of cDNAs under control of the cytomegalovirus (CMV) immediate-early promoter. Transfection of pRPneoCMV for expression of the chloramphenicol acetyltransferase (CAT) gene in several human cell lines showed that the CMV promoter is more efficient than the HIV-1 and RSV LTRs in directing gene expression from episomal vectors. In 293 human cells pRPneoCMV/CAT is twenty times more active in CAT expression than the well known pSV2CAT vector in COS7 cells. Stable expression of the gene of the herpes simplex virus type 1 and type 2 glycoprotein G, cloned into pRPneoCMV, was obtained in 293 cells. This vector will allow direct cloning of newly synthesized cDNAs whose expression can be monitored in human cells.

BK Virus

Tyrosine phosphorylation regulates the DNA binding activity of a nuclear factor 1-like repressor protein.

We have previously identified an ubiquitous repressor binding site that binds a nuclear factor 1 (NF-1)-like transcription factor designated BEF-1. The DNA binding activity of BEF-1, a 98-kDa protein, is increased by the oncoproteins of adenovirus, the early region 1a proteins (E1a), which results in the induction of further repression. Using the prototype repressor sequence, first identified in the enhancer of the human polyoma virus BKV-P2 we have shown that phosphorylation of BEF-1 is required for its DNA binding activity. We demonstrate here that the inhibition of DNA binding by BEF-1 dephosphorylated with potato acid phosphatase or calf intestinal alkaline phosphatase was reversed by sodium orthovanadate, a specific inhibitor of phosphotyrosyl-protein phosphatases. In addition, BEF-1 binding activity, but not the binding of related factor NF-1, could be inhibited by dephosphorylation with a specific phosphotyrosine phosphatase. We found that both polyclonal and monoclonal phosphotyrosine-specific antibodies blocked binding of the repressor protein to the BEF-1 site. Moreover, BEF-1 activity could be adsorbed on an anti-phosphotyrosine antibody column and specially eluted with phosphotyrosine. In transfection studies in HeLa cells, which contain high levels of BEF-1, we show that E1a-induced repression mediated by BEF-1 was relieved with the tyrosine kinase inhibitors genistein and tyrphostin. Together, these results demonstrate that a phosphotyrosine on the BEF-1 repressor protein regulates DNA binding activity and thus regulates repression of the BKV-P2 enhancer. This report represents the first demonstration that the phosphorylated state of a tyrosine can control gene expression by altering the DNA binding activity of a transcription factor.

BK Virus

Infection of human polyomaviruses JC and BK in peripheral blood leukocytes from immunocompetent individuals.

Widely disseminated infection with the human polyomaviruses JC and BK is followed by lifelong asymptomatic viral persistence that can be reactivated under prolonged immunosuppression to fatal CNS and urogenital disease. In an attempt to understand the pathogenesis of polyomavirus diseases, we asked whether leukocytes are involved in polyomavirus infection in the immunocompetent host. Peripheral blood leukocytes from 29 immunocompetent individuals and umbilical cord blood from 10 newborn children were analyzed for the presence of polyomavirus DNA. Southern blot analysis demonstrated the presence of JCV-specific full-length virus genomes and indicated involvement of the second human polyomavirus BK. In contrast to specimens from newborn children, PCR amplification of target DNA in the adult age group followed by species-specific hybridization provided evidence of concomitant JCV and BKV infection in almost all specimens. Nucleotide sequencing of virus-specific products representing DNA segments essential for virus multiplication confirmed presence of both virus species in leukocytes. The detection of a new virus subtype and single base changes or deletions in the noncoding DNA region from individual cases suggested widespread heterogeneity in the circulating virus population, although the structure of the transcriptional control elements in all cases was comparable to highly active elements found in lytically infected cells. Those findings and the localization of both virus types in the nuclei of blood cells by in situ hybridization demonstrate that JCV and BKV frequently infect peripheral leukocytes and give strong evidence that leukocytes are common sites of polyomavirus persistence in healthy individuals.

BK Virus