Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2009 Nov;83(21):10846-56.
doi: 10.1128/JVI.00542-09. Epub 2009 Jul 29.

Regulation of gene expression in primate polyomaviruses

Martyn K White  1 , Mahmut Safak, Kamel Khalili
Affiliations
Review

Regulation of gene expression in primate polyomaviruses

Martyn K White et al. J Virol. 2009 Nov.

Abstract

Polyomaviruses are a growing family of small DNA viruses with a narrow tropism for both the host species and the cell type in which they productively replicate. Species host range may be constrained by requirements for precise molecular interactions between the viral T antigen, host replication proteins, including DNA polymerase, and the viral origin of replication, which are required for viral DNA replication. Cell type specificity involves, at least in part, transcription factors that are necessary for viral gene expression and restricted in their tissue distribution. In the case of the human polyomaviruses, BK virus (BKV) replication occurs in the tubular epithelial cells of the kidney, causing nephropathy in kidney allograft recipients, while JC virus (JCV) replication occurs in the glial cells of the central nervous system, where it causes progressive multifocal leukoencephalopathy. Three new human polyomaviruses have recently been discovered: MCV was found in Merkel cell carcinoma samples, while Karolinska Institute Virus and Washington University Virus were isolated from the respiratory tract. We discuss control mechanisms for gene expression in primate polyomaviruses, including simian vacuolating virus 40, BKV, and JCV. These mechanisms include not only modulation of promoter activities by transcription factor binding but also enhancer rearrangements, restriction of DNA methylation, alternate early mRNA splicing, cis-acting elements in the late mRNA leader sequence, and the production of viral microRNA.

PubMed Disclaimer

Figures

FIG. 1.
FIG. 1.
Comparison of the genomes of JCV, BKV, and SV40. The circular genomes of the three polyomaviruses are shown as a linear schematic diagram (not to scale) with the NCCR at the center flanked by the coding regions—the early region on the left, which is transcribed from right to left, and the late region on the right, which is transcribed left to right. The early region of each virus encodes two primary regulatory proteins, large T antigen (LT-Ag) and small t antigen (Sm t-Ag). JCV and SV40 early regions also encode additional regulatory proteins. JCV encodes T′135, T′136, and T′165 (119), and SV40 encodes an additional 17-kDa protein (130). The late region of each virus, on the other hand, encodes three structural capsid proteins (VP1, VP2, and VP3). SV40 has also recently been shown to encode an additional very late protein, VP4, which functions in virus-mediated cell lysis (21). The late coding region of each virus also encodes a regulatory protein known as agnoprotein (Agno). The far 3′ region of LT-Ag of each virus was shown to encode pre-miRNAs that give rise to regulatory miRNAs (107, 112). Also shown in the NCCR are regions with dyad symmetry (DS), true palindromes (TP), poly(A/T) tract (AT), tandem repeats (TR), nontandem repeats (nTR), and the origin of viral DNA replication (Ori). Numbering for each virus is based on the Mad-1 strain of JCV (GenBank accession no. NC_001699, formerly J02226), the Dunlop strain of BKV (NC_001538, formerly J02038), and the 776 strain of SV40 (NC_001669, formerly J02400).
FIG. 2.
FIG. 2.
Multiple sequence alignment for early proximal part of the NCCR. CLUSTAL multiple sequence alignment was performed for JCV, BKV, and SV40 using the GenBank entries specified in the legend to Fig. 1. Sequences in red are shared for all three viruses and are also indicated with an asterisk. Sequences shared between JCV and BKV are in blue. Nonmatching sequences are in green. The underlined CAT corresponds to the opposite-strand ATG start codon for the early genes. Experimentally verified binding sites are shown for NF-κB (single underline) and C/EBPβ (double underline). Numbering is relative to the Mad-1 strain of JCV (GenBank accession no. NC_001699).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Abend, J. R., and M. J. Imperiale. 2008. Transforming growth factor-beta-mediated regulation of BK virus gene expression. Virology 378:6-12. - PMC - PubMed
    1. Abend, J. R., J. A. Low, and M. J. Imperiale. 2007. Inhibitory effect of gamma interferon on BK virus gene expression and replication. J. Virol. 81:272-279. - PMC - PubMed
    1. Abend, J. R., A. E. Joseph, D. Das, D. B. Campbell-Cecen, and M. J. Imperiale. 2009. A truncated T antigen expressed from an alternatively spliced BK virus early mRNA. J. Gen. Virol. 90:1238-1245. - PMC - PubMed
    1. Agostini, H. T., C. F. Ryschkewitsch, and G. L. Stoner. 1998. Rearrangements of archetypal regulatory regions in JC virus genomes from urine. Res. Virol. 149:163-170. - PubMed
    1. Akan, I., I. K. Sariyer, R. Biffi, V. Palermo, S. Woolridge, M. K. White, S. Amini, K. Khalili, and M. Safak. 2006. Human polyomavirus JCV late leader peptide region contains important regulatory elements. Virology 349:66-78. - PubMed

Publication types

LinkOut - more resources