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Y Yogo

Publications and source records attributed to Y Yogo.

At least 55 records · Page 3Linked to original sources

DNA-sequence rearrangement required for the adaptation of JC polyomavirus to growth in a human neuroblastoma cell line (IMR-32).

Infection of a human neuroblastoma cell line (IMR-32) with the JC polyomavirus (JCV) strain Mad-1 with subsequent serial passage results in the generation of a virus adapted to growth in IMR-32 (K. Akatani, M. Imai, M. Kimura, K. Nagashima, and N. Ikegami, J. Med. Virol., in press). To understand the basis of this adaptation, we molecularly cloned JCV DNAs from the adapted virus. The cloned JCV DNAs consisted of essentially three species (M1-IMRa, -IMRb, and -IMRc) with rearranged regulatory regions. Two TATA sequences are present in the regulatory region of the parental virus Mad-1, but one distal from the origin of replication was commonly deleted in M1-IMRa, -IMRb, and -IMRc. We showed that these regulatory regions were required for the efficient growth of JCV in IMR-32. Various JCV strains should be propagated in IMR-32, if their regulatory regions are replaced with those defined in this study. Since it is difficult to propagate JCV in cells other than primary human fetal glial cells, this system may be useful for structural and immunological studies of JCV.

Adaptation, Biological↗

Molecular characterization of a JC virus (Sap-1) clone derived from a cerebellar form of progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease caused by polyomavirus JC (JCV). In the majority of cases of PML the cerebrum is mainly affected (cerebral PML) but on rare occasions lesions are restricted to the cerebellum and brain stem (cerebellar PML). We report a rare cerebellar PML case which occurred in a Japanese patient undergoing prolonged hemodialysis treatment. To understand the molecular basis of the viral tissue tropism, we molecularly cloned JCV DNA and compared it with those of cerebral PML. Of ten clones analyzed nine showed identical fragment patterns after digestion with various restriction endonucleases, and we designated these clones Sap-1. It could be shown that the basic structures of the regulatory regions are similar between Sap-1 and isolates from cerebral PML. Restriction endonuclease mapping analysis was used to examine the genetic relationship between Sap-1 and urine-derived isolates containing the archetypal regulatory sequence. We found that Sap-1 was genetically related to an archetypal JCV isolate in Japan.

Base Sequence↗

Persistence of archetypal JC virus DNA in normal renal tissue derived from tumor-bearing patients.

JC virus DNAs derived from the urine of nonimmunosuppressed individuals generally contain an archetypal regulatory region which may have generated various regulatory regions of JC virus from from the brain with progressive multifocal leukoencephalopathy (PML). In this study, we examined whether JC virus persisting in normal human kidney tissue contains the archetypal regulatory region. Renal medulla, cortex, and tumor from 32 patients bearing renal tumors were screened for JC virus DNA by blot hybridization. Viral DNA was detected in the medulla in 13 cases (41%), in the cortex in 2 cases (6%), but not at all from the tumor. A number of viral DNA-positive specimens (8 from the medulla and 2 from the cortex) were used to amplify and sequence viral regulatory regions by polymerase chain reaction. Structures of the regulatory regions from all the specimens were, with a few nucleotide variations, identical with that of the archetypal region which was previously detected in the JC virus DNA from urine. This finding supports the hypothesis that the JC virus associated with PML evolved from the archetypal JC virus during persistence in human hosts. Furthermore, we present evidence that renal JCV is replicating and that progeny virions are excreted into the urine.

Adult↗

Typing of human polyomavirus JC virus on the basis of restriction fragment length polymorphisms.

JC virus DNA clones from the urine of nonimmunosuppressed Japanese individuals regularly contain an archetypal regulatory sequence which may have generated various regulatory sequences of JC virus isolates from patients with progressive multifocal leukoencephalopathy (PML). In this study, we established 15 new clones from the urine of Dutch, German, and Taiwanese healthy volunteers and patients. Most of these clones contained regulatory sequences essentially identical to the archetypal regulatory sequence. These clones, along with two representative urine-derived clones in Japan and five clones from the brains of PML patients (four established in the United States and one established in Japan), were analyzed with a number of restriction enzymes. We found nine restriction fragment length polymorphisms by which all clones were classified into either of the two types, A and B. Type A contained only clones from the West, while type B contained some from the West and all from eastern Asia. Each type contained both urine-derived and PML-derived clones. Furthermore, there was a close relationship between some urine-derived clones and some PML-derived clones in restriction site mapping analysis. These findings support the adaptation hypothesis which has been postulated to explain the genesis of PML-type JC viruses.

Base Sequence↗

Sequence rearrangement in JC virus DNAs molecularly cloned from immunosuppressed renal transplant patients.

From nonimmunocompromised individuals, we have recently identified a possible archetypal JC virus DNA sequence from which various regulatory sequences of JC virus isolates derived from patients with progressive multifocal leukoencephalopathy (PML) could have evolved. In this study, we analyzed the regulatory sequences of JCV DNAs cloned from urine samples of a PML risk group (renal transplant patients on immunosuppressive therapy). A number of JC virus DNAs were molecularly cloned from virions excreted in the urine of eight patients. Furthermore, fragments containing the regulatory region were amplified by the polymerase chain reaction and subsequently molecularly cloned from cell-associated JC virus excreted in the urine of two patients. The regulatory regions in all clones were analyzed with restriction enzymes, and those in representative clones were sequenced. We found that clones with the archetypal regulatory sequence were predominant in all urine samples, but a few clones carried regulatory sequences that diverged from the archetypal sequence by deletion or duplication. The finding that sequence rearrangement in the archetypal regulatory region occurs in the course of infection in immunosuppressed hosts is consistent with the adaptation hypothesis which has been put forward to explain the divergence of the regulatory regions in PML-derived JC virus isolates.

Base Sequence↗

Regulatory DNA sequence conserved in the course of BK virus evolution.

Within the genome of human polyomavirus BK (BKV), there exists a noncoding regulatory region toward the late region side of the origin of DNA replication. In most BKV strains isolated by viral culture, this regulatory region contains tandem repeats varying in size. Recently, however, several laboratories isolated new BKV strains (designated as archetypal strains) lacking such repeat sequences. To examine the genetic relationship between archetypal strains, a phylogenetic tree was constructed for seven BKV strains, including three archetypal strains, from DNA sequence data on the late genes, those for leader protein (agnoprotein), and those for structural proteins (VP1, VP2, and VP3). For three strains data previously reported were used, whereas for the others sequences were determined in this study. From total numbers of nucleotide substitutions in each pair of strains, a phylogenetic tree was constructed by the unweighted pair-group method. The phylogenetic tree obtained reveals that BKV strains containing the archetypal regulatory region do not constitute a cluster of closely related strains and that these strains, together with those carrying the major part of the archetypal regulatory region, are widespread in the BKV population. This finding suggests that the basic structure of the archetypal regulatory region has been conserved in the course of BKV evolution.

BK Virus↗

High incidence of urinary JC virus excretion in nonimmunosuppressed older patients.

Urine specimens from 120 patients attending urologic clinics were screened by blot hybridization for the presence of a polyomavirus DNA. Detected viral DNA was then identified as BK or JC by fine restriction enzyme analysis. BK and JC viral DNA was found in 5 (4%) and 35 (29%) patients, respectively. Detection rates were compared among three age groups: 0-29, 30-59, and 60-89 years. Detection of JC viral DNA increased with age and reached the highest value (45%) in the group aged 60-89 years. For BK viral DNA a correlation between detection and age was not clear because the rate of detection was low, although the highest rate (9%) occurred in the oldest group. To confirm the active urinary excretion of polyomavirus DNA in older patients, urine specimens from 23 patients (60-90 years) treated at an internal medicine clinic were examined for viral DNA. BK and JC viral DNA were in 2 (9%) and 12 patients (52%), respectively. These results suggest that JC virus is frequently reactivated in older individuals.

Adolescent↗

Isolation of a possible archetypal JC virus DNA sequence from nonimmunocompromised individuals.

We molecularly cloned JC polyomavirus DNAs from urine samples of eight nonimmunosuppressed patients and two healthy individuals. The cloned viral DNAs all contained an archetypal regulatory sequence from which various regulatory sequences of JC polyomavirus isolates derived from patients with progressive multifocal leukoencephalopathy could have evolved by deletion and amplification.

Base Sequence↗

Growth efficiency of naturally occurring BK virus variants in vivo and in vitro.

We molecularly cloned a number of BK virus (BKV) DNAs from urine samples collected from a patient with systemic lupus erythematosus undergoing immunosuppressive therapy. On the basis of the structure of the noncoding regulatory region, cloned viral DNAs were classified into a major group and several minor groups. The major group contained a single 68-base-pair (bp) promoter-enhancer element and a 63-bp sequence identified in the genomes of many BKV strains. Most of the minor groups retained a variety of duplications within the transcriptional control region and the origin of DNA replication. We assayed various cloned viral DNAs for the capacity to induce viral growth in transfected human embryonic kidney cells. While major viral DNAs induced slow viral replication, a minor viral DNA retaining partial duplication of the 68-bp element induced rapid viral growth. We concluded that reiteration of the promoter-enhancer element, which is required for efficient growth of BKV in cell culture, is not advantageous for replication of BKV in natural hosts.

BK Virus↗

[Bladder carcinoma in situ which harbored human papilloma virus. A case report].

Last year, we reported that human papilloma virus type 16 genome (HPV 16 genome) was detected in a case (S.Y.) of bladder carcinoma in situ (bladder CIS) (Cancer Res., 1988). Since then, a number of bladder tumors other than CIS were searched for HPV genome. However, no HPV genome was detected in the bladder tumors. From the results, we consider that HPV may not have a relation with all types of bladder tumor but with only a part of it. In the current report, the case (S.Y.) is presented more precisely than before, in particular on the characteristic bladder lesion. The patient was a 40-year-old female with immunodeficiency and anemia who was referred from a hospital with a complaint of asymptomatic pyuria. Cystoscopic examination revealed a bladder tumor, well-demarcated, white and velvety lesion with slight elevation. On November 25, 1987, she underwent total cystectomy, resection of the anterior vaginal wall and of a part of vulval skin, and ileal conduit formation. Postoperative course was stormy because of bleeding from the wounds and thrombophlebitis in the right femoral vein. In spite of the episodes, she eventually recovered and was discharged 2 months later. However she was readmitted 9 months later due to severe anemia which was ascribed to acute myelogenous leukemia. She is now on cancer chemotherapy for leukemia.

Adult↗

Distribution of varicella-zoster virus strains carrying a PstI-site-less mutation in Japan and DNA change responsible for the mutation.

We have analyzed 53 varicella-zoster virus (VZV) strains isolated in Japan for the presence of a PstI cleavage site in a middle portion of the long unique region of VZV genome. About 25% of the strains examined did not have this PstI cleavage site, although the majority of strains retained this site. For several VZV strains lacking this PstI cleavage site, we sequenced a recombinant DNA-derived short segment containing the mutation. In all strains analyzed, we identified a base replacement from A to G within the PstI recognition sequence. Because no wild-type VZV strain carrying this mutation has been found so far in other countries, it is very likely that the mutation once occurred in the past and has been conserved in some strains in Japan. We have concluded that the PstI-site-less mutation is reliable marker for discrimination of VZV strains in Japan.

DNA, Viral↗

Presence of human papillomavirus type 16 genome in bladder carcinoma in situ of a patient with mild immunodeficiency.

Using blot hybridization, we analyzed 10 bladder tumors (1 transitional cell carcinoma in situ, 1 adenocarcinoma, and 8 papillary tumors) for the presence of human papillomavirus (HPV) DNA. We detected HPV 16 DNA in a transitional cell carcinoma in situ, whereas no HPV DNA was found in the other bladder tumors. The patient, a 40-year-old female, who harbored HPV 16 DNA in the bladder tumor, had mild immunodeficiency and recently suffered from the bladder tumor, common warts on the right hand, Bowen's disease of the vulva, and severe dysplasia of the vaginal wall. From each of these lesions, we detected the DNA of HPV 16 or an unclassified HPV. HPV DNAs existed in nonintegrated form in all lesions examined. To our knowledge, this is the first case in which a bladder tumor was shown to harbor HPV DNA. However, HPV does not seem to be regularly present in bladder tumor, because we could not detect HPV DNA from the most common bladder tumor, i.e., papillary tumor. Our demonstration of HPV 16 DNA in a transitional cell carcinoma in situ of the bladder suggests that HPV may be associated with some of the bladder tumors of this type.

Adult↗

Variation of R1 repeated sequence present in open reading frame 11 of varicella-zoster virus strains.

We molecularly cloned the tandem direct reiteration (R1) present in open reading frame (ORF) 11 from three independent strains of varicella-zoster virus. Comparison of the R1 sequences among varicella-zoster virus strains revealed that, although the portion of R1 near the 5' terminus of ORF 11 was conserved among strains, the 3'-terminal portion varied remarkably. This variation was due to the different arrangement of two elements (A and B) and a segment produced by fusion of A and B and to a single-base change in the A element. Since the difference in the size of R1 among strains was a multiple of 3 base pairs, the variation in R1 caused no frame shift in ORF 11.

DNA, Recombinant↗

Strain variation of R5 direct repeats in the right-hand portion of the long unique segment of varicella-zoster virus DNA.

We located a region of interstrain size variability in a short segment in an area at the right-hand end of the long unique sequence of the varicella-zoster viral genome. Varicella-zoster virus strains isolated in a district of Japan were classified into three groups on the basis of the size of this segment. Sequence comparison of the variable segment among strains from different groups revealed that the tandem direct repeat, R5, in the segment was variable among strains. R5, which was first discovered in a European strain (Dumas), contained a direct duplication of 88-base-pair (bp) elements separated by a 24-bp element (A.J. Davison and J.E. Scott, J. Gen. Virol. 67:1759-1816, 1986). We found that one 88-bp element and one 24-bp element constitute a repeating unit whose copy number varied from one to three among strains. The simplest R5 we detected was similar to that of Dumas, but there were a few base mismatches between these two R5 structures.

Base Sequence↗

Genome variation among varicella-zoster virus isolates derived from different individuals and from the same individuals.

We have used 12 restriction enzymes to analyse the DNA of 24 clinical isolates of VZV derived from 12 patients in order to compare isolates derived from different individuals and derived serially from the same individual. As reported previously, only a small proportion of the isolates differed with respect to the presence or absence of restriction sites. However, we found that the size of DNA fragments generated from all the isolates derived from different patients varied in any of four regions, one of which was first recognized in this study. In one case, where multiple isolates recovered from the same individual were analysed, each was distinguished from the others not only by differences in the variable regions but also by the presence or absence of a restriction site in a nonvariable region. This suggests that multiple strains of VZV can be present in the same human host.

Chickenpox↗

Detection of varicella-zoster virus DNA in cultured cells and tissue specimens by in situ hybridization using biotin-labeled probes.

A method of in situ hybridization with biotinylated probes is described for specific detection of varicella-zoster virus (VZV) DNA in infected cell cultures and in human biopsied or autopsied materials. From molecularly cloned EcoRI-fragments of VZV DNA, we selected as probes for in situ hybridization three fragments (B, H, and K) which had any detectable homology neither with human cell DNA nor with DNAs of VZV-related viruses (herpes simplex virus type 1, type 2 and human cytomegalovirus). The procedure of in situ hybridization was based on that of Brigati et al. (Virology 126, 32-50, 1983), but following modifications were made. 1) The concentration of probe DNA was lowered to 100 ng per ml. 2) Streptavidin-biotin system was used for detection of hybridization. 3) Acid phosphatase was used to generate color development discernible from melanin present in skin. 4) Before hybridization, deparaffinized sections were treated with trypsin by the procedure routinely employed for detection of viral antigens in paraffin-embedded sections.

Cells, Cultured↗

Sequence reiteration required for the efficient growth of BK virus.

Compared with wild-type BK virus DNA having tandem triplication of a 68 base pair (bp) element in its transcriptional control region, a mutant viral DNA with a single copy of the 68 bp element induced remarkably delayed virus production in human embryonic kidney (HEK) cells. We molecularly cloned the DNA of progeny viruses using plasmid vector pAT153. Nucleotide sequence analysis of representative clones revealed that all of the altered viral DNAs examined duplicated various segments extending over origin-distal portions of the 68 bp element and their flanking regions. After transfection of HEK cells, most of these rearranged viral DNAs induced viral growth slightly slower than, or at the same rate as, the wild-type viral DNA. Comparison of the structures of these rearranged viral DNAs suggests that reiteration of a 13 bp sequence, which is located in an origin-distal portion of the 68 bp element, is required for the efficient replication of BK virus.

BK Virus↗