Biomedical subjects

Harutaka Katano

Publications and source records attributed to Harutaka Katano.

At least 19 recordsLinked to original sources

PubMed2025

Identification of Novel Wraparound Transcripts in JC Polyomavirus.

JC polyomavirus (JCPyV) is a ubiquitous pathogen that causes progressive multifocal leukoencephalopathy (PML). Although a recent study using next-generation sequencing (NGS) provided detailed transcriptome atlases for polyomaviruses (PyVs) such as BK polyomavirus and simian virus 40, the transcriptome of JCPyV remains poorly characterized. Here, we conducted a comprehensive analysis using both short-read and long-read NGS technologies to construct a transcriptome atlas of JCPyV. RNA extracted from IMR-32 and HEK293 cells transfected with the circular JCPyV genome was analyzed, leading to the identification of 39 previously uncharacterized viral transcripts in addition to 12 known ones. Among the novel transcripts, we identified wraparound transcripts, conserved across PyVs, which are generated through continuous, multicyclic transcription of the circular viral genome. These included both late transcripts containing leader-to-leader repeated sequences and SuperT transcripts with multiple LxCxE motifs. Notably, wraparound transcripts, including SuperT transcripts, were also detected in brain tissues from PML patients. Collectively, this study significantly expands our understanding of the JCPyV transcriptome, revealing the expression of wraparound transcripts in PML lesions. These findings provide valuable insights into the molecular basis of JCPyV gene expression and PML pathogenesis, potentially facilitating the development of effective countermeasures against PML.

JC Virus↗

PubMed2006

Pathogenesis of cytomegalovirus-associated labyrinthitis in a guinea pig model.

Cytomegalovirus infects fetuses through the placenta, resulting in various congenital disorders in newborns, including hearing loss. We developed a monoclonal antibody to guinea pig cytomegalovirus (GPCMV) that was available for immunohistochemistry, and investigated the expression of the GPCMV antigen in animal models of direct and congenital infections. Injection of GPCMV, directly to the inner ear, increased the sound pressure level and resulted in labyrinthitis with severe inflammation. Immunohistochemistry detected GPCMV-infected cells mainly in the scala tympani, scala vestibule and spinal ganglion, but rarely in the cochlear duct. Injection of GPCMV to 5-week pregnant guinea pigs resulted in severe labyrinthitis in fetuses. Immunohistochemistry detected GPCMV-infected cells in the perilymph area and spinal ganglion, but not in the endolymph area, including hair cells. These data suggest that the virus spreads via the perilymph and neural routes in the inner ear of both models of direct and congenital infections.

Animals↗

PubMed2006

Potential role of natural killer cells in controlling growth and infiltration of AIDS-associated primary effusion lymphoma cells.

Natural killer (NK) cells are an important component of the innate immune response against microbial infections and tumors. Direct involvement of NK cells in tumor growth and infiltration has not yet been demonstrated clearly. Primary effusion lymphoma (PEL) cells were able to produce tumors and ascites very efficiently with infiltration of cells in various organs of T-, B- and NK-cell knock-out NOD/SCID/gammac(null) (NOG) mice within 3 weeks. In contrast, PEL cells formed small tumors at inoculated sites in T- and B-cell knock-out NOD/SCID mice with NK-cells while completely failing to infiltrate into various organs. Immunosupression of NOD/SCID by treatment with an antimurine TM-beta1 antibody, which transiently abrogates NK cell activity in vivo, resulted in enhanced tumorigenicity and organ infiltration in comparison with non-treated NOD/SCID mice. Activated human NK cells inhibited tumor growth and infiltration in NOG mice. Our results suggest that NK cells play an important role in growth and infiltration of PEL cells, and activated NK cells could be a promising immunotherapeutic tool against tumor or virus-infected cells either alone or in combination with conventional therapy. The rapid and efficient engraftment of PEL cells in NOG mice also suggests that this new animal model could provide a unique opportunity to understand and investigate the mechanism of pathogenesis and malignant cell growth.

Acquired Immunodeficiency Syndrome↗

PubMed2006

Expression of Kaposi's sarcoma-associated herpesvirus-encoded K10/10.1 protein in tissues and its interaction with poly(A)-binding protein.

The K10/10.1 protein is encoded by a cluster of interferon regulatory factor (IRF) homologues in the Kaposi's sarcoma-associated herpesvirus (KSHV, human herpesvirus 8, HHV-8) genome. In the present study, we showed that an anti-K10 antibody reacted with a 110-kDa protein encoded by the K10/10.1 gene of KSHV in KSHV-infected primary effusion lymphoma (PEL) cell lines. Expression of K10/10.1 protein was induced by phorbol ester in KSHV-infected cells. A reporter gene assay demonstrated that K10/10.1 protein did not influence promoter activity of human interferon genes, regardless of its homology to human IRFs. Poly(A)-binding protein (PABP) was identified as a partner of K10/10.1 protein. Immunoprecipitation revealed that K10/10.1 protein interacted with PABP specifically in PEL cell lines. IFA revealed co-localization of K10/10.1 protein and PABP in the nucleus of KSHV-infected cells. These data suggest that K10/10.1 protein may affect the translational status or stability of mRNA in host cells.

Amino Acid Sequence↗

PubMed2006

Thymus-derived leukemia-lymphoma in mice transgenic for the Tax gene of human T-lymphotropic virus type I.

Adult T-cell leukemia-lymphoma (ATLL) is a group of T-cell malignancies caused by infection with human T-lymphotropic virus type I (HTLV-I). Although the pathogenesis of ATLL remains incompletely understood, the viral regulatory protein Tax is centrally involved in cellular transformation. Here we describe the generation of HTLV-I Tax transgenic mice using the Lck proximal promoter to restrict transgene expression to developing thymocytes. After prolonged latency periods, transgenic mice developed diffuse large-cell lymphomas and leukemia with clinical, pathological and immunological features characteristic of acute ATLL. Transgenic mice were functionally immunocompromised and they developed opportunistic infections. Fulminant disease also developed rapidly in SCID mice after engraftment of lymphomatous cells from transgenic mice. Flow cytometry showed that the cells were CD4(-) and CD8(-), but CD44(+), CD25(+) and cytoplasmic CD3(+). This phenotype is indicative of a thymus-derived pre-T-cell phenotype, and disease development was associated with the constitutive activation of NF-kappaB. Our model accurately reproduces human disease and will provide a tool for analysis of the molecular events in transformation and for the development of new therapeutics.

Animals↗

PubMed2006

Decrease in Epstein-Barr virus-positive AIDS-related lymphoma in the era of highly active antiretroviral therapy.

Recent introduction of highly active antiretroviral therapy (HAART) is reported to have reduced the incidence of lymphoma among HIV-infected individuals. A clinicopathological study was performed on 86 AIDS-related lymphoma patients who were treated in Tokyo area from 1987 to 2005. The incidence of lymphoma detected by autopsy was 27% (53 cases/198 autopsies). Diffuse large B cell lymphoma was the most predominant histological subtype throughout the period (78%). Burkitt's lymphoma (BL) increased from 2% in the pre-HAART era (before end-1997) to 13% in the HAART era, whereas incidence of BL did not vary between HAART users and non-users. Epstein-Barr virus (EBV)-positive lymphoma decreased from 88% in the pre-HAART era to 58% in the HAART era, but did not differ significantly between HAART users (73%) and non-users (74%). Nodal involvement of lymphoma increased from 14% in the pre-HAART era to 50% in the HAART era; however, central nervous system involvement decreased from 62 to 38%. Kaposi's sarcoma-associated herpesvirus infection was rare (4%) among all cases. These data suggest that HAART might play a partial role in these changes, and the alteration in immunological backgrounds, such as EBV prevalence, is suggested as another leading cause of these changes in Japanese AIDS-related lymphoma.

Adolescent↗

PubMed2006

Quantitative analysis of Kaposi sarcoma-associated herpesvirus (KSHV) in KSHV-associated diseases.

BACKGROUND: Accurate numbers of copies of Kaposi sarcoma-associated herpesvirus (KSHV) and numbers of virus-infected cells in lesions caused by KSHV-associated diseases are unknown. METHODS: Quantitative polymerase chain reaction (PCR) and computerized imaging of immunohistochemical analysis were performed on pathologic sections of samples from persons with KSHV-associated diseases. RESULTS: Real-time PCR and semiquantitative PCR-Southern blotting demonstrated that DNA extracted from biopsy samples of KS lesions contained approximately 1-2 viral copies/cell. KSHV-associated lymphoma contained 10-50 viral copies/cell. Computerized-image analysis demonstrated that approximately 49% of cells expressed KSHV-encoded latency-associated nuclear antigen in KS biopsy samples. On the basis of results of real-time PCR and computerized-image analysis, the predicted number of viral copies was 3.2 viral copies/cell in KS lesions. Computerized-image analysis also revealed that the expression of open-reading frame (ORF)-50 protein, an immediate early protein of KSHV, was very rare in KS lesions, which implies that they were mainly composed of proliferating cells latently infected with KSHV. In multicentric Castleman disease lesions, 25% of virus-infected cells expressed ORF50 protein, which suggests the frequent lytic replication of KSHV. CONCLUSIONS: Numbers of viral copies and of virus-positive cells vary among KSHV-associated diseases, which suggests different mechanisms of viral pathogenesis. The combination of real-time PCR and computerized-image analysis provides a useful tool for the assessment of the number of viral copies in KSHV-associated diseases.

Herpesviridae Infections↗

PubMed2006

Distinct expression of Kaposi's sarcoma-associated herpesvirus-encoded proteins in Kaposi's sarcoma and multicentric Castleman's disease.

The expression of Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8)-encoded proteins is herein demonstrated in Kaposi's sarcoma (KS) and multicentric Castleman's disease (MCD) in a single lymph node derived from a patient with acquired immunodeficiency syndrome. Immunohistochemistry revealed that both lytic and latent KSHV proteins were expressed in cells of the MCD lesion. KSHV-encoded viral interleukin-6 was also detected in follicular dendritic cells of the germinal center. Cytoplasmic localization of open reading frame 59 protein and latency-associated nuclear antigen suggested KSHV activation in the MCD lesion. Moreover, a high copy number of KSHV was detected in the blood. Clinically, pegylated-liposomal doxorubicin induced regression of not only KS, but also lymphadenopathy of the MCD lesion with a decrease in KSHV load and human interleukin-6 in the blood. To the best of the authors' knowledge this is the first case demonstrating differential expression of virus proteins in two KSHV-associated diseases, KS and MCD, in the same section. The case confirms lytic KSHV infection in MCD, and suggests that clinical symptoms of MCD might be closely linked with KSHV activation.

Adult↗

PubMed2006