Common and unique features of T antigens encoded by the polyomavirus group

Abstract

Although 12 different members of the polyomavirus group have now been identified, only SV40 and PyV have been studied extensively. Whereas each member of the group shows a restricted host range, viruses infecting species from birds to humans have been reported. Although little is known concerning the biology of natural infections in the wild, it is apparent that these viruses exhibit various cell-type tropisms. Some viruses, such as LPV (B lymphocytes) or KV (pulmonary endothelium), are tightly restricted to specific cell types, while others, such as PyV, infect a variety of tissues in the animal. Despite these differences, all polyomaviruses share a common strategy of productive infection, expressing T antigens which act both on cellular targets, preparing cellular metabolism for supporting optimal viral replication, and then on targets within the viral genome, to regulate viral DNA replication, transcription, and assembly. Presumably, this common replication strategy restricts the degree to which the sequences of these viruses can diverge. Thus, sequence motifs conserved among these different viruses may indicate key structural elements essential for biochemical function. In this article I have compared the sequences of all polyomavirus-encoded large and small T antigens sequenced to date. This has led to the following conclusions and speculations. (i) Comparison of the domain organization of different large T antigens reveals that these proteins fall into two structural classes. Members of the SV40 class, which include SV40, JCV, BKV, and SA12, possess a carboxyl-terminal domain, which in SV40 has been shown to be dispensable for viral DNA replication but essential for virion assembly. The PyV class lacks the carboxyl-terminal domain and carries additional amino acids within the amino-terminal domain. When total amino acid identity is examined, members of the SV40 class show the highest degree of conservation (65 to 85%), while sequence identity among the remaining viruses varies from 18 to 55%. (ii) The DNA binding domains of most large T antigens are closely related, with amino acid identities ranging from 35 to 86%. Several residues within this domain are invariant among all T antigens. All of these viruses have multiple copies of the consensus T-antigen-binding pentanucleotide (GAGGC) in their ori region, suggesting that all T antigens recognize this sequence. The single exception is the large T antigen encoded by the avian virus BFDV. The putative DNA binding domain of this protein shows little or no sequence relation to that of other T antigens. Furthermore, the GAGGC motif is not found in the ori region of this virus.(ABSTRACT TRUNCATED AT 400 WORDS)

Prevalence and molecular characterization of WU/KI polyomaviruses isolated from pediatric patients with respiratory disease in Thailand

“…The zinc finger motif was found in WU polyomaviruses at amino acid residues C321, C324, H336 and H339 whereas KI polyomaviruses displayed it at amino acid residues C312, C315, H327 and H331 of the LTAg protein. Conserved motifs "GPINSGKT" (amino acid positions 443-450) and "GSVKVNLE" (amino acid positions 520-527) were detected in all WU polyomaviruses analyzed whereas the motifs "GPINSGKT" (amino acid positions 436-443) and "GCVEVNLE" (amino acid positions 513-520) were found in all KI polyomaviruses analyzed in this study (Pipas, 1992).…”

Identification and analysis of a retinoblastoma binding motif in the replication protein of a plant DNA virus: requirement for efficient viral DNA replication.

“…Identification it (Rybicki, 1994). Similarly, within the papovavirus group the large majority of its members contain a typical LXCXE motif, but, for example, the T-ag of avian budgerigar fledging disease virus, which shows the lowest homology with the T-ag of other members, contains a C->A change within its Rb binding motif (Pipas, 1992). This may reflect that the C residue seems to be less critical for Rb binding, as is also the case in our experiments, where a C->G change reduced significantly, but did not abolish completely, the ability of WDV Rep to interact with Rb.…”

Identification of a Novel Polyomavirus from Patients with Acute Respiratory Tract Infections

“…Splicing to a conserved splice acceptor site would generate a predicted protein of 648 amino acids ( Table 1). The predicted WU virus LTAg contained conserved features common to T antigens, including a DnaJ domain in the N terminus with the highly conserved hexapeptide motif HPDKGG; the LxCxE motif necessary for binding Rb; a canonical DNA binding domain; a zinc finger region; and conserved motifs GPXXXGKT and GXXXVNLE in the ATPase-p53 binding domain [22].…”

“…Based on comparative sequence analysis of LTAgs, the polyomaviruses are classified into two subclasses: a primatelike group exemplified by SV40, and a mouse polyoma-like group exemplified by murine polyoma virus [22]. Using these criteria, the T antigen of WU appeared to more closely resemble the mouse polyoma-like class of virus than the primate class.…”