ABSTRACT
Polyomaviruses have the following properties: small size of the virion (diameter 40-45 nm), naked icosahedral capsid, superhelical double-strand circular DNA genome of molecular weight 3.2 x 106, shared nucleotide sequences with other polyomaviruses, and nuclear site of multiplication. The nonenveloped virion has icosahedral symmetry and 72 pentameric capsomers. The virion is made up of protein (88%) and a single copy of a circular double-stranded DNA molecule (12%), which has about 5,300 base pairs.1,5 The viral genome is functionally divided into (i) a noncoding control region (NCCR) (0.4 kb), (ii) an early coding region (2.4 kb), which codes for tumors antigens: large T (T-ag), middle T (in mouse and hamster viruses), and small T (t-ag), and (iii) a late coding region (2.3 kb), which codes for viral capsid proteins VP1, VP2, and VP3 and agnoprotein. The NCCR is located between the early and late regions and contains the T-ag binding sites. It contains (i) the origin of DNA replication (ori) and (ii) the regulatory regions for early and late transcription control sequences during viral life cycle (Fig. I).6 The sequence blocks in NCCR are arbitrarily referred to by the alphabetical designations P, Q, R, and S. These blocks serve as regulatory regions, or enhancer elements, and are believed to contain several transcription factor binding sites, which putatively modulate viral transcription. Naturally occurring BKV strain in the kidney and urine usually have an archetypal regulatory region.6"8
The early and late coding regions are transcribed from different strands of the DNA molecule. The direction of early and late transcrip tion is divergent, with opposite strands participating in these processes, starting from the origin of replication. T-ag is a multifunctional protein with distinct ability to bind host cell regulatory proteins. T-ag controls both viral DNA replication, and gene transcription, and interferes with host cell transcription factors.9,10 During replication, viral DNA associates with host cell histones to form mini viral chromosomes, which are structurally indistinguishable from host cell chromatin.11,12 Each pentamer of the viral icosahedron consists of five VP 1 molecules and one molecule ofVP2 or VP3. VP1 [molecular mass (mm) 39,600] is the major capsid protein (accounts for more than 70% of the virion
♦Nasimul Ahsan-Professor of Medicine, Mayo Clinic - College of Medicine 4205 Belfort Road, Suite 1100, Jacksonville, Florida 32216-5876, USA. Email: ahsan.nasimul@mayo.edu
Chronic AUograft Failure: Natural History, Pathogenesis, Diagnosis and Management, edited by Nasimul Ahsan. ©2008 Landes Bioscience.
