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PubMed1989

Characterization of a new polyomavirus (Polyomavirus papionis-2) isolated from baboon kidney cell cultures.

Viruses with papovavirus morphology were seen in fluids from baboon kidney cell cultures on three separate occasions (isolates A, B, and C). The size of the virions, 47.9 nm, placed the virus in the polyomavirus genus. It grew well in baboon kidney and Vero cells and less well in human embryo lung (HEL) fibroblasts. The virus could not be identified as the previously described baboon polyomavirus, SA 12, or as any of the other known primate polyomaviruses BK, JC or SV 40, the non-primate viruses mouse polyoma, K, rabbit kidney vacuolating virus (RKV) or bovine polyomavirus (FRKV) by immunofluorescence, immune electron microscopy or hemagglutination inhibition (HI) tests. A rabbit antiserum to the new virus (isolate A) reacted only with the three isolates and not with the other primate polyomaviruses studied. Thirteen percent of 118 wild-caught baboons (Papio anubis) had HI antibody to the new polyomavirus and 21 percent were seropositive for SA 12; only two baboons had antibody to both viruses. These results suggest that in baboons there are two antigenically distinct polyomaviruses which circulate independently. The two viruses may also be distinguished by their hemagglutinating properties: SA 12 agglutinated erythrocytes from a wider range of species but only the newly recognized polyomavirus agglutinated baboon erythrocytes. We propose that the two baboon viruses, SA 12 and the new virus, should be named Polyomavirus papionis-1 and Polyomavirus papionis-2 respectively.

Animals↗

PubMed1987

Anti-idiotypic antibodies to a polyomavirus monoclonal antibody recognize cell surface components of mouse kidney cells and prevent polyomavirus infection.

Anti-idiotypic antibodies have been successfully used to identify and isolate the receptor for several cell ligands. To prepare an immunologic probe for identification of the polyomavirus receptor on mouse kidney cells, polyclonal antisera against antipolyomavirus antibodies were prepared in rabbits. Fab fragments of the previously characterized monoclonal antibody E7, which neutralizes polyomavirus infection, were used for immunization (S. J. Marriott and R. A. Consigli, J. Virol. 56:365-372, 1985). Sera containing the greatest anti-idiotype activity were identified by enzyme-linked immunosorbent assay (ELISA) and purified by a series of affinity columns. The anti-idiotypic antibodies recognized the E7 idiotope in an ELISA, and anti-idiotype binding could be inhibited by preincubation of E7 monoclonal antibody with polyomavirus virions. When mixed with anti-idiotype immunoglobulin G (IgG), E7 was no longer capable of binding or immunoprecipitating polyomavirus virions or neutralizing polyomavirus infection. Direct immunofluorescence showed anti-idiotype IgG reactivity with a cell surface component of mouse kidney cells. Anti-idiotype F(ab')2 effectively competed with polyomavirus for binding to mouse kidney cells and displayed binding kinetics similar to those of polyomavirus. Virus infection of mouse kidney cells was blocked in a dose-dependent manner following treatment of the cells with anti-idiotype IgG. The anti-idiotype identified several proteins (95, 50, and 24 to 31 kilodaltons) in an immunoblot of mouse kidney cell membrane proteins but reacted predominantly with a single 50-kilodalton protein in a radioimmunoassay. The anti-idiotype failed to react with virus proteins in three assays, including ELISA, immunoprecipitation, and immunoblotting. The implications of this work for future identification and characterization of the polyomavirus receptor on mouse kidney cells are discussed.

Animals↗

PubMed1989

Asp-286----Asn-286 in polyomavirus large T antigen relaxes the specificity of binding to the polyomavirus origin.

We isolated revertants of a polyomavirus whose origin of DNA replication contains a point mutation in the palindrome to which large T antigen binds. Four independent second-site revertants contain an Asp-286----Asn-286 substitution in large T antigen. This mutant large T antigen activates replication of DNAs containing the mutant polyomavirus origin as well as replication of DNAs containing the wild-type origin; however, replication of DNAs with enhancer mutations is not activated by this large T antigen. The Asn-286 mutation occurs in a positively charge region of large T antigen near the location of several mutations which inactivate DNA replication. We suggest that this region of large T antigen is responsible for recognition of specific DNA sequences at the origin and that ionic forces are important for this interaction.

Amino Acid Sequence↗

PubMed2026

Binding capacity of Intravenous immunoglobulin G to BK polyomavirus determines its anti-BK polyomavirus activity in infected cultures.

BK polyomavirus (BKPyV) causes disease in immunocompromised individuals. This study tested the hypothesis that the antiviral efficacy of intravenous immunoglobulin (IVIG) against BKPyV depends on the relationship between its virus-binding capacity and the viral burden. We first quantified the BKPyV-binding capacity of IVIG and then characterized BKPyV replication in kidney-derived HK-2 and HEK293 cells and in HEL cells under IVIG treatment. Subsequently, we analyzed the efficacy of IVIG at 0.03-10 mg/mL against low-multiplicity of infection (MOI) and high-MOI infection in relation to the BKPyV-binding capacity of IVIG. BKPyV productively infected all three cell lines, with 14-day replication cycles of 2.2, 4.0, and 7.0 in HK-2, HEK293, and HEL cells, respectively, indicating that HEL cells were the most permissive. IVIG bound approximately 108 copies of BKPyV DNA per milligram. In the low-MOI infection model, where the total viral load remained within this estimated binding capacity, IVIG showed clear neutralizing activity, significantly reducing viral spread, viral DNA levels, and the number of VP1-positive cells in a dose-dependent manner (p < 0.001). In contrast, in the high-MOI infection model, the viral load appeared to be high relative to the estimated IVIG binding capacity even at 10 mg/mL, and IVIG showed little or no neutralizing effect on viral production or spread of infected cells. These findings identify an experimental relationship between IVIG binding capacity, viral burden, and antiviral efficacy and suggest that the antiviral effect of IVIG is greatest when administered early, thereby supporting further clinical evaluation of early or preemptive IVIG administration.

Humans↗

PubMed1989

Polyomavirus genome and polyomavirus enhancer-driven gene expression during myogenesis.

The mRNAs for myogenic functions are coordinately transcribed with polyomavirus (Py) early mRNA during in vitro differentiation of mouse C2 myoblast cells. Sequence analysis shows that the A domain of the Py enhancer includes an E1A-like consensus sequence that is also found in the 5' upstream region of two genes expressed during myoblast differentiation: alpha-actin and myosin light chain. Therefore, the coordinate expression of such genes with Py early mRNA may be activated by a common cellular regulatory factor. In the present work, we report that C2 cells surviving Py infection are unable to differentiate and do not express alpha-actin and myosin light-chain mRNAs. Hybrids between such Py-resistant myoblast cells and the parental cells exhibited dominance of the permissibility to Py growth and of the expression of myogenic mRNAs. In C2 cells transiently transfected with a chimeric plasmid (pSVPy12CAT) harboring the bacterial chloramphenicol acetyltransferase (CAT) gene driven by the Py enhancer-promoter region, the CAT gene was expressed irrespective of their stage of differentiation. Moreover, undifferentiated stably transfected cells expressing the CAT gene restricted viral growth. Py-resistant C2 myoblasts transiently transfected with pSVPy12CAT also expressed the CAT gene driven by the Py enhancer. This contradictory finding is similar to results previously obtained by other investigators with cloned genes specific for myogenic functions, and it may be explained by a structural difference between the pSVPy12CAT and the Py genomic organizations in which the viral enhancer operates.

Animals↗

PubMed1992

Induction of polyomavirus DNA replication by carcinogens in polyomavirus-transformed rat cells: evidence that the viral enhancer is not the primary target in the induction pathway.

In the polyomavirus (Py)-transformed rat cell line designated LPT, replication of the integrated Py DNA can be induced by exposure of the cells to carcinogens. In view of the observation that enhancer elements are essential components of the Py origin of replication, it appeared plausible that the induction is triggered by synthesis or modification of an enhancer-binding protein which is required for activation of the viral origin. To test this hypothesis, we have used a plasmid containing a modified Py origin (test plasmid), in which the Py enhancer has been replaced with five repeats of the yeast GAL4 upstream activating sequence, and a plasmid encoding the GAL4 transcriptional activator protein. Previous studies in which these two plasmids were cotransfected into mouse cells that are permissive for Py showed that the GAL4 protein can transactivate the modified Py origin and cause replication of the test plasmid. When similar cotransfection assays were performed in LPT cells, no replication of the test plasmid was observed unless the cells were exposed to the carcinogen mitomycin C subsequent to the transfection, in which case replication of the test plasmid was induced. Control experiments showed that even though the GAL4 protein was required for the induction, its concentration was not affected by the exposure to mitomycin C. These results indicate that the primary target in the induction pathway is not an enhancer-binding protein; instead, the induction appears to be triggered by changes in other components of the replication initiation complex which may be associated with the origin core.

Animals↗

PubMed1975

Evidence of chronic persistent infections with polyomaviruses (BK type) in renal transplant recipients.

Ten renal transplant recipients showing a significant increase in human polyomavirus antibodies, indicative of an acute infection, were followed up serologically over periods ranging from two months to more than two years. Fifty-four serum specimens were available for the study and they were tested by both haemagglutination-inhibition and complement-fixation. Polyomavirus antigens were prepared from the BK and SV40-like strains of polyomaviruses, and from the SV40 virus. One strain of polyomavirus, related to the BK strain was isolated from the urine of one of these patients. Two other BK strains were recovered from the urine and kidney, respectively, of transplant recipients not included in this study. Sera of these two patients were not obtained until the transplantation was made; they were already highly positive for polyomavirus antibodies, precluding the demonstration of an increase in antibody titer. Serologic results have shown that HAI antibodies persist at high titers throughout the observation period. This persistence ranged from two to four months (four cases), seven to eleven months (three cases) and thirteen to twenty months (three cases). In none of the cases could a decrease of high titer be demonstrated. Moreover, density gradient studies have shown that specific IgM antibodies also tend to persist over many months. Similar serologic results were obtained in complement-fixation tests with a BK antigen. Titers were at least 1 in 30 in the study group, but were not observed among healthy blood donors. All sera were uniformly negative for SV40 and SV40-like antigens. One polyomavirus isolation was successful from urine obtained six months after initial serologic evidence for a polyomavirus infection. The other two viruses were isolated from materials taken four and seven months after first detection of polyomavirus antibodies at high titer. Both serologic evidence and viral isolations seem to indicate that polyomaviruses (BK type) might cause a chronic infection in humans.

Animals↗

PubMed1986

Construction of a helper-free recombinant adenovirus that expresses polyomavirus large T antigen.

Adenovirus-polyomavirus recombinant viruses were constructed in vitro by inserting a hybrid transcription unit composed of the adenovirus type 2 major late promoter and the early coding region of polyomavirus into the adenovirus type 5 vector Ad5 delta E1/dl309. The vector lacks the E1a and E1b transcription units and contains a unique restriction endonuclease cleavage site in their place. The polyomavirus genomic insert contained a small deletion which precluded the synthesis of functional small and middle T antigen but allowed for the synthesis of large T antigen. One recombinant virus, Ad5PyR39, which contained the hybrid transcription unit in the opposite transcriptional orientation from the overall direction of late-gene transcription, was studied in detail. Ad5PyR39 replicated efficiently without a helper virus in human 293 cells and expressed hybrid mRNAs of the expected size and composition that were translated to yield large T antigen. The large T antigen synthesized in 293 cells was the same size as that produced in mouse 3T6 cells lytically infected with polyomavirus, and this protein bound efficiently and specifically to the large-T-antigen-binding sites in polyomavirus DNA. Moreover, the large T antigen encoded by the recombinant virus proved capable of catalyzing the replication in mouse 3T6 cells of a plasmid containing the polyomavirus origin for DNA replication. Comparison of the amount of large T antigen produced in 3T6 cells infected with polyomavirus with that in 293 cells infected with Ad5PyR39, under optimal conditions for each system, revealed at least a fivefold greater yield of the protein on a per cell basis in the latter system compared with the former. Ad5PyR39 should prove to be useful to isolate large quantities of functional polyomavirus large T antigen for structural and biochemical studies.

Adenoviridae↗

PubMed1987

Octyl-beta-D-glucopyranoside extracts polyomavirus receptor moieties from the surfaces of mouse kidney cells.

Polyomavirus receptor moieties were extracted from the surfaces of mouse kidney cells with the nonionic detergent octyl-beta-D-glucopyranoside. Following extraction with this detergent, mouse kidney cells were refractory to polyomavirus infection. Binding studies demonstrated that this loss of susceptibility resulted from extraction of a peripheral membrane protein or proteins required for proper virus attachment to and infection of mouse kidney cells. Infection of extracted mouse kidney cells returned following a 2-h recovery period. However, the presence of cycloheximide or tunicamycin in the recovery media interfered with recovery from infection. Cells could be infected immediately after extraction by supplying them with the extracted moieties prior to or concomitant with infection. A complex of polyomavirus and the extracted receptor protein was formed by in vitro incubation and was stable in sucrose gradient analysis. Functional receptor moieties were prepared in the form of liposomes from the detergent extract. The virus-receptor complex was immunoprecipitated with anti-polyomavirus immunoglobulin G, and the portion of the complex contributed by the cell was identified. Immunoblot analysis of the mouse kidney cell detergent extract with a receptor-specific 125I-labeled anti-idiotypic antibody or 125I-labeled polyomavirus demonstrated several reactive proteins. Attachment of polyomavirus to mouse kidney cells, followed by extraction of the virus-receptor complex, identified polyomavirus-binding proteins similar to those observed in in vitro binding. Proteins with molecular weights of approximately 95,000, 50,000 and 25,000 to 30,000 were consistently observed in all receptor assays. The relationship between these proteins and their possible involvement as the cell receptor for polyomavirus are discussed.

Animals↗

PubMed1991

Mouse DNA primase plays the principal role in determination of permissiveness for polyomavirus DNA replication.

We have investigated the species-specific replication of polyomavirus DNA in the cell-free system that was established previously (Y. Murakami, T. Eki, M. Yamada, C. Prives, and J. Hurwitz, Proc. Natl. Acad. Sci. USA 83:6347-6351, 1986). Extracts from various species of cells supported polyomavirus DNA replication in a species-specific manner that was consistent with the host range specificity of polyomavirus; extracts prepared from mouse and hamster cells were active, whereas extracts prepared from human, monkey, and insect cells were inactive. The addition of DNA polymerase alpha-primase purified from mouse cells induced the replication of polyomavirus DNA in a cell-free system containing polyomavirus large tumor antigen and nonpermissive cell extracts, such as human and insect cell extracts. Isolated mouse DNA primase alone also induced polyomavirus DNA replication in human cell extracts but not in insect cell extracts, indicating that mouse DNA primase plays the principal role in determining permissiveness for polyomavirus DNA replication.

Animals↗

PubMed1985

Control of Polyomavirus T-antigen and DNA synthesis in mouse embryo fibroblast cells by vitamin A.

Vitamin A (retinoic acid, 10(-6) M) treatment of confluent mouse embryo cells for only 7 h resulted in optimal inhibition of Polyomavirus replication. Depending upon the input multiplicity of virus, one could wait until between 12 and 18 h postinfection to add vitamin A and still observe maximal inhibition of virus yields. Taken together, and assuming the same kinetics before and after virus infection, these results suggested that the inhibitory action of vitamin A occurred between 19 and 25 h into the Polyomavirus replication cycle. In this model system, such a time corresponded to the onset of T-antigen expression and virus-induced cellular DNA synthesis. Analysis of both viral and virus-induced cellular DNA synthesis by the method of Hirt (J. Mol. Biol., 26: 365-369, 1967) and by cesium chloride gradients suggested that vitamin A preferentially inhibited viral, more than virus-induced cellular, DNA synthesis in confluent cell monolayers. Vitamin A also concomitantly inhibited Polyomavirus T-antigen expression in such confluent cultures. In contrast, viral DNA synthesis and infectious virus yields were not significantly inhibited by vitamin A in subconfluent cell cultures. The antagonistic effect of vitamin A on Polyomavirus replication in confluent monolayers could be blocked with cycloheximide, a reversible protein synthesis inhibitor. This suggested that vitamin A inhibition of Polyomavirus replication was indirect and mediated by a newly synthesized protein. Taken together, these results suggest that vitamin A induced a protein in confluent, but not subconfluent, cells, which blocked the expression of Polyomavirus T-antigen. Decreased amounts of T-antigen most likely reduced Polyomavirus and cellular DNA synthesis and virus yield.

Animals↗

PubMed1986

Cloning and characterization of budgerigar fledgling disease virus, an avian polyomavirus.

The DNA of a virus isolated from fledgling budgerigars, designated BFDV, was cloned and analyzed with regard to its relationship to the polyomavirus subgroup of the papovavirus family. Under relaxed conditions, the DNA of BFDV cross-hybridized with the DNAs of members of the polyomavirus subgroup, such as the mouse polyomavirus, the monkey viruses simian virus 40, stump-tailed macaque virus, and lymphotropic papovavirus, and the human viruses JCV and BKV. Under stringent conditions, however, no homologies could be detected. Furthermore, BFDV propagated in chicken embryo cells was antigenically related to the capsid antigen(s) of the other polyomaviruses. The virus was able to transform hamster embryo cells in vitro which is a typical feature of polyomaviruses. These data clearly indicate that BFDV is a new distinct member of the polyomavirus genus representing the first nonmammalian polyomavirus.

Animals↗

PubMed1988

The genome of budgerigar fledgling disease virus, an avian polyomavirus.

Budgerigar fledgling disease virus (BFDV) represents the first avian member of the Polyomavirus family. In contrast to mammalian polyomaviruses BFDV exhibits unique biological properties, in particular it is able to cause an acute disease with distinct organ manifestations in affected birds. Here we present the complete nucleotide sequence of the BFDV genome, consisting of 4980 bp. When compared to published nucleotide sequences of other polyomaviruses, the BFDV genome exposes a number of very similar structural features, and undoubtedly qualifies as a member of that family of viruses. The most important differences include a large T antigen remarkably reduced in size, and an origin of replication region with fundamental deviations from the origin structure of all other polyomaviruses. The specific characteristics of the BFDV genome may be used to place this virus into a distinct subgroup within the Polyomavirus family and may give a clue to the elucidation of its extraordinary biological properties.

Amino Acid Sequence↗

PubMed1987

Overproduction of polyomavirus middle T antigen in mammalian cells through the use of an adenovirus vector.

To overproduce biologically active polyomavirus middle T antigen, we used an adenovirus vector and human 293 cells as hosts. Two helper-independent recombinant adenoviruses were isolated that contain a hybrid transcription unit, in differing orientations, at a site in the adenovirus genome from which the E1a and most of the E1b transcription units have been deleted. The hybrid transcription unit consists of the adenovirus type 2 major late promoter and tripartite leader and a cDNA segment capable of encoding polyomavirus middle T antigen and accompanying 3' RNA-processing signals. Both recombinant viruses were stable and replicated to high titers in human 293 cells. The polyomavirus sequences were expressed, predominantly at late times after infection of 293 cells, to yield mRNAs that encoded middle T antigen. One of the recombinant viruses also expressed a middle T antigen-related protein in 293 cells. The latter was translated from one of several novel mRNA species that resulted from aberrant splicing and incomplete RNA processing of precursor RNA transcripts. Comparison of the amount of middle T antigen produced in 3T6 cells infected with polyomavirus with that in 293 cells infected with either of the recombinant adenoviruses, under optimal conditions for each system, revealed at least a 10-fold greater yield of the protein on a per-cell basis in the latter system than in the former. The recombinant-virus-encoded middle T antigen was biologically active, as evidenced by its ability to associate with and serve as a substrate for human pp60c-src. The functionality of the middle T antigen was further confirmed by demonstrating that both recombinant viruses efficiently transformed Rat-1 cells. These recombinant viruses will be useful to overproduce middle T antigen and to introduce the polyomavirus oncogene into a wide variety of mammalian cells.

Adenoviruses, Human↗

PubMed1986

Recombinant retroviruses encoding simian virus 40 large T antigen and polyomavirus large and middle T antigens.

We used a murine retrovirus shuttle vector system to construct recombinants capable of constitutively expressing the simian virus 40 (SV40) large T antigen and the polyomavirus large and middle T antigens as well as resistance to G418. Subsequently, these recombinants were used to generate cell lines that produced defective helper-free retroviruses carrying each of the viral oncogenes. These recombinant retroviruses were used to analyze the role of the viral genes in transformation of rat F111 cells. Expression of the polyomavirus middle T antigen alone resulted in cell lines that were highly tumorigenic, whereas expression of the polyomavirus large T resulted in cell lines that were highly tumorigenic, whereas expression of the polyomavirus large T resulted in cell lines that were unaltered by the criteria of morphology, anchorage-independent growth, and tumorigenicity. More surprisingly, SV40 large T-expressing cell lines were not tumorigenic despite the fact that they contained elevated levels of cellular p53 and had a high plating efficiency in soft agar. These results suggest that the SV40 large T antigen is not an acute transforming gene like the polyomavirus middle T antigen but is similar to the establishment genes such as myc and adenovirus EIa.

Animals↗

PubMed1986

Binding of polyomavirus large T antigen to the human hsp70 promoter is not required for trans activation.

Polyomavirus large T antigen binds to two sites located between positions -110 and -170 of a human heat shock protein 70 (hsp70) promoter. Methylation interference studies show that binding for each site is determined by two GPuGGC pentanucleotide sequences. The specificity of this binding interaction is similar to that observed for large T binding to the viral genome. The existence of sequences that bind a viral protein in a cellular promoter raises the possibility that these sequences play a role in gene expression in an uninfected cell. We show that hsp70 large T antigen binding site 1 is capable of functioning as an upstream promoter element in cells that do not contain any viral T antigen. Genetic analysis of this effect suggests that a cellular factor exists that has a binding specificity that overlaps but is not identical to that of polyomavirus large T antigen. To determine whether binding of polyomavirus large T antigen can regulate expression of the intact human hsp70 promoter, we have introduced the promoter into mouse cells with plasmids that express the polyomavirus early proteins. These proteins stimulate the level of correctly initiated hsp70 transcripts, but surprisingly the degree of stimulation remains unchanged for promoter constructs in which the large T antigen binding sites have been deleted. These observations suggest that trans activation of the hsp70 promoter by the polyomavirus early proteins occurs through protein-protein interactions and not through sequence-specific DNA binding.

Acetyltransferases↗

PubMed1992

Retinoic acid receptor alpha suppresses polyomavirus transformation and c-fos expression in rat fibroblasts.

To explore the molecular mechanisms by which retinoic acid inhibits oncogenic transformation, we have examined the effects of retinoic acid on the polyomavirus-induced transformation of rat fibroblasts. Treatment of rat F111 fibroblasts with high concentrations of retinoic acid (10(-6) M) partially inhibited the ability of polyomavirus to induce dense focus formation (50-70%). This effect was not secondary to a retinoic acid-dependent block of cellular proliferation. To address the role of the retinoic acid receptor (RAR-alpha) in mediating the transformation-inhibitory effect of retinoic acid, we have overexpressed either RAR-alpha or cellular retinoic acid-binding protein I (CRABP) cDNAs in F111 cells. Introduction of a CRABP I expression vector did not alter the responsiveness of F111 cells to retinoic acid in any detectable fashion. In contrast, overexpression of RAR-alpha increased the sensitivity of F111 cells to the transformation-inhibitory action of retinoic acid by 10- to 100-fold. At high concentrations, retinoic acid inhibited transformation of F111-RAR cells by polyomavirus by about 90%. At near physiological concentrations, retinoic acid inhibited transformation by 25-50% in F111-RAR cells but not in control cells. Retinoic acid did not inhibit either the synthesis of polyoma middle T (mT) or pp60c-src, the cellular target for mT action, or the formation of mT:pp60c-src:PI-3 kinase (phosphatidylinositol-3 kinase) complexes. Therefore, RAR-alpha was not acting as a negative regulator of expression of either the polyomavirus middle T oncogene or the cellular proto-oncogene, c-src. It seems likely that RAR-alpha regulates the expression of cellular genes whose products interact in some way with mT-regulated signaling pathways, leading to a ligand-dependent suppression of polyoma transformation. In addition, RAR-alpha overexpression selectively inhibits the serum-stimulated expression of the c-fos gene, but does not affect the expression of a number of other serum- and polyomavirus-inducible genes including c-jun, junB, c-myc and actin.

Animals↗

PubMed1991

Nucleotide sequence and genome organization of the murine polyomavirus, Kilham strain.

The polyomavirus Kilham strain (KV) represents a second murine member of the polyomavirus family. However, in contrast to other polyomaviruses, KV exhibits a stringent host and cell specificity. To determine the relationship of these viruses, the complete DNA sequence of KV consisting of 4754 bp was determined. The predicted organization of K virus was found to be comparable to that of other members of the polyomavirus family with two strands coding in an opposite direction of an intergenic region harboring putative control elements for gene expression. These include consensus elements for the origin of DNA replication as well as predicted promoter protein binding domains. Inferred signal sequences for 3' and 5' end formation of mRNAs and splice/branch site consensus sequences resemble those found among the SV40 group of viruses. From the organization of the genome two nonstructural proteins, large T and small t antigen, are predicted, both of which share the same amino-terminal sequence. Three putative capsid proteins VP1, VP2, and VP3 are encoded by alternative open reading frames. The nucleotide sequence in the proposed origin of DNA replication and the inferred amino acid sequence of the viral proteins suggest an evolutionary relationship placing KV between the murine PyV and the SV40 group of viruses. In the region bearing putative transcriptional control elements less nucleotide similarity to that of other polyomaviruses is found and this may reflect the unique host and cell specificity of KV.

Amino Acid Sequence↗