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10. Endogenous non-retroviral RNA virus elements in mammalian genomes

Author

Horie, Masayuki, Honda, Tomoyuki, Suzuki, Yoshiyuki, Kobayashi, Yuki, Daito, Takuji, Oshida, Tatsuo, Ikuta, Kazuyoshi, Jern, Patric, Gojobori, Takashi, Coffin, John M., and Tomonaga, Keizo

Subjects
DNA -- Health aspects -- Chemical properties, Genomics -- Research, RNA viruses -- Physiological aspects -- Properties, Mammals -- Genetic aspects -- Health aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Retroviruses are the only group of viruses known to have left a fossil record, in the form of endogenous proviruses, and approximately 8% of the human genome is made up of these elements (1,2). Although many other viruses, including non-retroviral RNA viruses, are known to generate DNA forms of their own genomes during replication (3-5), none has been found as DNA in the germline of animals. Bornaviruses, a genus of non-segmented, negative-sense RNA virus, are unique among RNA viruses in that they establish persistent infection in the cell nucleus (6-8). Here we show that elements homologous to the nucleoprotein (N) gene of bornavirus exist in the genomes of several mammalian species, including humans, non-human primates, rodents and elephants. These sequences have been designated endogenous Borna-like N (EBLN) elements. Some of the primate EBLNs contain an intact open reading frame (ORF) and are expressed as mRNA. Phylogenetic analyses showed that EBLNs seem to have been generated by different insertional events in each specific animal family. Furthermore, the EBLN of a ground squirrel was formed by a recent integration event, whereas those in primates must have been formed more than 40 million years ago. We also show that the NmRNA of a current mammalian bornavirus, Borna disease virus (BDV), can form EBLN-like elements in the genomes of persistently infected cultured cells. Our results provide the first evidence for endogenization of non-retroviral virus-derived elements in mammalian genomes and give novel insights not only into generation of endogenous elements, but also into a role of bornavirus as a source of genetic novelty in its host., Bornaviruses are the only animal RNA viruses that achieve a highly cell-associated fife cycle within the nuclear envelope (6-9), and can therefore provide not only new models of RNA virus [...]

Published
2010
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11. Two Different Strains of Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) in North and South Osaka by Phylogenetic Analysis of Evolutionary Lineage: Evidence for Independent SFTSV Transmission

Author

Ikemori, Ryo, primary, Aoyama, Ikuko, additional, Sasaki, Tadahiro, additional, Takabayashi, Hirono, additional, Morisada, Kazutoshi, additional, Kinoshita, Masaru, additional, Ikuta, Kazuyoshi, additional, Yumisashi, Takahiro, additional, and Motomura, Kazushi, additional

Published
2021
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12. Ongoing rubella epidemic in Osaka, Japan, in 2018–2019

Author

Kanbayashi, Daiki, primary, Kurata, Takako, additional, Kubo, Hideyuki, additional, Kaida, Atsushi, additional, Yamamoto, Seiji, additional, Egawa, Kazutaka, additional, Hirai, Yuki, additional, Okada, Kazuma, additional, Ikemori, Ryo, additional, Yumisashi, Takahiro, additional, Yamamoto, Akira, additional, Yoshida, Hideki, additional, Hirayama, Takanori, additional, Ikuta, Kazuyoshi, additional, and Motomura, Kazushi, additional

Published
2020
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14. Positive and negative aspects of the human immunodeficiency virus protease: development of inhibitors versus its role in AIDS pathogenesis

Author

Ikuta, Kazuyoshi, Suzuki, Satoko, Horikoshi, Haruko, Mukai, Tetsu, and Luftig, Ronald B.

Subjects
HIV (Viruses) -- Physiological aspects, AIDS (Disease) -- Physiological aspects, Proteases -- Physiological aspects, Enzyme inhibitors -- Physiological aspects, Medical case management -- Analysis, Biological sciences
Abstract

This review elaborates on the role of HIV proteases in the viral morphogenesis as well as those of specific proteases and mutated particles promoting AIDS pathogenesis. Also, the use and mechanism of action of combinatorial inhibitors, targeting different viral proteins, and HIV protease inhibitors are discussed.

Published
2000

16. Poly (I:C), an agonist of toll-like receptor-3, inhibits replication of the Chikungunya virus in BEAS-2B cells

Author

Li Yong-Gang, Siripanyaphinyo Uamporn, Tumkosit Uranan, Noranate Nitchakarn, A-nuegoonpipat Atchareeya, Pan Yang, Kameoka Masanori, Kurosu Takeshi, Ikuta Kazuyoshi, Takeda Naokazu, and Anantapreecha Surapee

Subjects
Chikungunya virus, Poly (I:C), BEAS-2B cells, TLR3, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background Double-stranded RNA (dsRNA) and its mimic, polyinosinic acid: polycytidylic acid [Poly (I:C)], are recognized by toll-like receptor 3 (TLR3) and induce interferon (IFN)-β in many cell types. Poly (I:C) is the most potent IFN inducer. In in vivo mouse studies, intraperitoneal injection of Poly (I:C) elicited IFN-α/β production and natural killer (NK) cells activation. The TLR3 pathway is suggested to contribute to innate immune responses against many viruses, including influenza virus, respiratory syncytial virus, herpes simplex virus 2, and murine cytomegalovirus. In Chikungunya virus (CHIKV) infection, the viruses are cleared within 7–10 days postinfection before adaptive immune responses emerge. The innate immune response is important for CHIKV clearance. Results The effects of Poly (I:C) on the replication of CHIKV in human bronchial epithelial cells, BEAS-2B, were studied. Poly (I:C) suppressed cytopathic effects (CPE) induced by CHIKV infection in BEAS-2B cells in the presence of Poly (I:C) and inhibited the replication of CHIKV in the cells. The virus titers of Poly (I:C)-treated cells were much lower compared with those of untreated cells. CHIKV infection and Poly (I:C) treatment of BEAS-2B cells induced the production of IFN-β and increased the expression of anti-viral genes, including IFN-α, IFN-β, MxA, and OAS. Both Poly (I:C) and CHIKV infection upregulate the expression of TLR3 in BEAS-2B cells. Conclusions CHIKV is sensitive to innate immune response induced by Poly (I:C). The inhibition of CHIKV replication by Poly (I:C) may be through the induction of TLR3, which triggers the production of IFNs and other anti-viral genes. The innate immune response is important to clear CHIKV in infected cells.

Published
2012
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17. Hepatitis E virus in Norway rats (Rattus norvegicus) captured around a pig farm

Author

Kanai Yuta, Miyasaka Satoshi, Uyama Sachiko, Kawami Sachiyo, Kato-Mori Yuko, Tsujikawa Muneo, Yunoki Mikihiro, Nishiyama Shoko, Ikuta Kazuyoshi, and Hagiwara Katsuro

Subjects
Medicine, Biology (General), QH301-705.5, Science (General), Q1-390
Abstract

Abstract Background Hepatitis E virus (HEV) transmitted via the oral route through the consumption of contaminated water or uncooked or undercooked contaminated meat has been implicated in major outbreaks. Rats may play a critical role in HEV outbreaks, considering their negative effects on environmental hygiene and food sanitation. Although the serological evidence of HEV infection in wild rodents has been reported worldwide, the infectivity and propagation of HEV in wild rats remain unknown. To investigate if rats are a possible carrier of HEV, we studied wild Norway rats (Rattus norvegicus) that were caught near a pig farm, where HEV was prevalent among the pigs. Methods We examined 56 Norway rats for HEV. RNA from internal organs was examined for RT-PCR and positive samples were sequenced. Positive tissue samples were incubated with A549 cell line to isolate HEV. Anti-HEV antibodies were detected by ELISA. Results Sixteen rats were seropositive, and the HEV RNA was detected in 10 of the 56 rats. Sequencing of the partial ORF1 gene from 7 samples resulted in partially sequenced HEV, belonging to genotype 3, which was genetically identical to the HEV prevalent in the swine from the source farm. The infectious HEVs were isolated from the Norway rats by using the human A549 cell line. Conclusions There was a relatively high prevalence (17.9%) of the HEV genome in wild Norway rats. The virus was mainly detected in the liver and spleen. The results indicate that these animals might be possible carrier of swine HEV in endemic regions. The HEV contamination risk due to rats needs to be examined in human habitats.

Published
2012
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19. Characterization of H5N1 influenza viruses isolated from humans in vitro

Author

Kameoka Masanori, Bai Gui-Rong, Kanai Yuta, Waicharoen Sunthareeya, Chittaganpitch Malinee, Li Yong-Gang, Takeda Naokazu, Ikuta Kazuyoshi, and Sawanpanyalert Pathom

Subjects
Infectious and parasitic diseases, RC109-216
Abstract

Abstract Since December 1997, highly pathogenic avian influenza A H5N1viruses have swept through poultry populations across Asian countries and been transmitted into African and European countries. We characterized 6 avian influenza H5N1 viruses isolated from humans in 2004 in Thailand. A highly pathogenic (HP) KAN353 strain showed faster replication and higher virulence in embryonated eggs compared to other strains, especially compared to the low pathogenic (LP) SP83 strain. HP KAN353 also showed strong cytopathogenicity compared to SP83 in Madin-Darby canine kidney cells. Interestingly, LP SP83 induced smaller plaques compared to other strains, especially HP KAN353. PB2 amino acid 627E may contribute to low virulence, whereas either PB2 amino acid 627 K or the combination of 627E/701N seems to be associated with high virulence. The in vitro assays used in this study may provide the basis for assessing the pathogenesis of influenza H5N1 viruses in vivo.

Published
2010
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20. High systemic levels of interleukin-10, interleukin-22 and C-reactive protein in Indian patients are associated with low in vitro replication of HIV-1 subtype C viruses

Author

Bala Manju, Nishihara Reiko, Arias Juan F, and Ikuta Kazuyoshi

Subjects
Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Background HIV-1 subtype C (HIV-1C) accounts for almost 50% of all HIV-1 infections worldwide and predominates in countries with the highest case-loads globally. Functional studies suggest that HIV-1C is unique in its biological properties, and there are contradicting reports about its replicative characteristics. The present study was conducted to evaluate whether the host cytokine environment modulates the in vitro replication capacity of HIV-1C viruses. Methods A small subset of HIV-1C isolates showing efficient replication in peripheral blood mononuclear cells (PBMC) is described, and the association of in vitro replication capacity with disease progression markers and the host cytokine response was evaluated. Viruses were isolated from patient samples, and the corresponding in vitro growth kinetics were determined by monitoring for p24 production. Genotype, phenotype and co-receptor usage were determined for all isolates, while clinical category, CD4 cell counts and viral loads were recorded for all patients. Plasmatic concentrations of cytokines and, acute-phase response, and microbial translocation markers were determined; and the effect of cytokine treatment on in vitro replication rates was also measured. Results We identified a small number of viral isolates showing high in vitro replication capacity in healthy-donor PBMC. HIV-1C usage of CXCR4 co-receptor was rare; therefore, it did not account for the differences in replication potential observed. There was also no correlation between the in vitro replication capacity of HIV-1C isolates and patients' disease status. Efficient virus growth was significantly associated with low interleukin-10 (IL-10), interleukin-22 (IL-22), and C-reactive protein (CRP) levels in plasma (p < .0001). In vitro, pretreatment of virus cultures with IL-10 and CRP resulted in a significant reduction of virus production, whereas IL-22, which lacks action on immune cells appears to mediate its anti-HIV effect through interaction with both IL-10 and CRP, and its own protective effect on mucosal membranes. Conclusions These results indicate that high systemic levels of IL-10, CRP and IL-22 in HIV-1C-infected Indian patients are associated with low viral replication in vitro, and that the former two have direct inhibitory effects whereas the latter acts through downstream mechanisms that remain uncertain.

Published
2010
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25. Interferon-alpha treatment leads to accumulation of virus particles on the surface of cells persistently infected with the human immunodeficiency virus type 1

Author

Yasuda, Yuko, Miyake, Shiro, Kato, Shiro, Kita, Masakazu, Kishida, Tunataro, Kimura, Takuro, and Ikuta, Kazuyoshi

Subjects
Antiviral agents -- Health aspects, AIDS (Disease) -- Research, HIV infection -- Research, Interferon alpha -- Health aspects, Health
Abstract

Interferon (IFN) is a substance produced by cells of the immune system which is known to have activity against viruses. IFN has been shown to suppress the production of the human immunodeficiency virus type 1 (HIV-1) in tissue culture (in the laboratory). Studies in mice show that IFN-alpha inhibits production of the virus in the body, but that the proteins of the virus are still synthesized. Virus particles are seen on the surface of infected cells that have been treated with IFN-alpha, but the viruses are not released from the cell surface. The effect of IFN-alpha on viral production in human cells that are either acutely infected with HIV-1 (producing virus for a short period of time, but in large quantities) or persistently infected with HIV-1 (producing virus for long periods of time, but in small quantities) was examined. There was suppression of virus in both types of cells. As seen in the mouse studies, the proteins of the virus were still produced, and the completed virus was found on the surface of infected cells. Thus, IFN-alpha appears to be involved in the suppression of the release of intact virus from infected cells. The results suggest that IFN-alpha may be useful in the treatment of individuals who are infected with HIV, and that it may suppress the occurrence of disorders that occur due to infection. (Consumer Summary produced by Reliance Medical Information, Inc.)

Published
1990

27. Diversity of antigenic mutants of influenza A(H1N1)pdm09 virus escaped from human monoclonal antibodies

Author

Yasuhara, Atsuhiro, primary, Yamayoshi, Seiya, additional, Soni, Priyanka, additional, Takenaga, Toru, additional, Kawakami, Chiharu, additional, Takashita, Emi, additional, Sakai-Tagawa, Yuko, additional, Uraki, Ryuta, additional, Ito, Mutsumi, additional, Iwatsuki-Horimoto, Kiyoko, additional, Sasaki, Tadahiro, additional, Ikuta, Kazuyoshi, additional, Yamada, Shinya, additional, and Kawaoka, Yoshihiro, additional

Published
2017
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30. Distribution and Propagation of Hepatitis E Virus in Experimentally Infected Swine

Author

OGIWARA, Katsuro, Iwabu, Yukie, Kanai, Yuta, Miyasho, Taku, Daidoji, Tomo, Yunoki, Mikihiro, Tsujikawa, Muneo, Ohkubo, Yuuji, Yasue, Hiroshi, and Ikuta, Kazuyoshi

Subjects
viruses, virus diseases, digestive system diseases
Abstract

HEV infections in human and pigs have been reported in many countries; however, the precise distribution and multiplication of this virus in the host remains poorly understood. In this study, we examined the distribution and multiplication of HEV genotype 3 in two piglets at the early phase of intravenous infection, and also examined the virus distribution in a naturally infected pig. We developed real-time RT-PCR to determine copy numbers of the HEV genome in the sera, feces and organs. HEV-RNA was detected in serum from a pig transiently for 7 days post-inoculation (dpi). The HEV copy numbers in the feces appearing 7 dpi were increased to 3.4x106 copies/g at 14 dpi. In contrast, the higher copy numbers of HEV were widely distributed in the tissue organs from naturally HEV-infected pig. The study showed that intravenously inoculated HEV was distributed in several restricted tissues, such as in the liver and intestine.

Published
2007

33. Novel Polymerase Gene Mutations for Human Adaptation in Clinical Isolates of Avian H5N1 Influenza Viruses

Author

Arai, Yasuha, primary, Kawashita, Norihito, additional, Daidoji, Tomo, additional, Ibrahim, Madiha S., additional, El-Gendy, Emad M., additional, Takagi, Tatsuya, additional, Takahashi, Kazuo, additional, Suzuki, Yasuo, additional, Ikuta, Kazuyoshi, additional, Nakaya, Takaaki, additional, Shioda, Tatsuo, additional, and Watanabe, Yohei, additional

Published
2016
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34. Correction for Okabayashi et al., Detection of Chikungunya Virus Antigen by a Novel Rapid Immunochromatographic Test

Author

Okabayashi, Tamaki, primary, Sasaki, Tadahiro, additional, Masrinoul, Promsin, additional, Chantawat, Nantarat, additional, Yoksan, Sutee, additional, Nitatpattana, Narong, additional, Chusri, Sarunyou, additional, Morales Vargas, Ronald E., additional, Grandadam, Marc, additional, Brey, Paul T., additional, Soegijanto, Soegeng, additional, Mulyantno, Kris Cahyo, additional, Churrotin, Siti, additional, Kotaki, Tomohiro, additional, Faye, Oumar, additional, Faye, Ousmane, additional, Sow, Abdourahmane, additional, Sall, Amadou Alpha, additional, Puiprom, Orapim, additional, Chaichana, Panjaporn, additional, Kurosu, Takeshi, additional, Kato, Seiji, additional, Kosaka, Mieko, additional, Ramasoota, Pongrama, additional, and Ikuta, Kazuyoshi, additional

Published
2016
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35. Characterization of H5N1 Influenza Virus Variants with Hemagglutinin Mutations Isolated from Patients

Author

Watanabe, Yohei, primary, Arai, Yasuha, additional, Daidoji, Tomo, additional, Kawashita, Norihito, additional, Ibrahim, Madiha S., additional, El-Gendy, Emad El-Din M., additional, Hiramatsu, Hiroaki, additional, Kubota-Koketsu, Ritsuko, additional, Takagi, Tatsuya, additional, Murata, Takeomi, additional, Takahashi, Kazuo, additional, Okuno, Yoshinobu, additional, Nakaya, Takaaki, additional, Suzuki, Yasuo, additional, and Ikuta, Kazuyoshi, additional

Published
2015
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36. Avian Influenza Virus Infection of Immortalized Human Respiratory Epithelial Cells Depends upon a Delicate Balance between Hemagglutinin Acid Stability and Endosomal pH

Author

Daidoji, Tomo, primary, Watanabe, Yohei, additional, Ibrahim, Madiha S., additional, Yasugi, Mayo, additional, Maruyama, Hisataka, additional, Masuda, Taisuke, additional, Arai, Fumihito, additional, Ohba, Tomoyuki, additional, Honda, Ayae, additional, Ikuta, Kazuyoshi, additional, and Nakaya, Takaaki, additional

Published
2015
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37. A novel immunochromatographic system for easy-to-use detection of group 1 avian influenza viruses with acquired human-type receptor binding specificity

Author

Watanabe, Yohei, primary, Ito, Tetsuo, additional, Ibrahim, Madiha S., additional, Arai, Yasuha, additional, Hotta, Kozue, additional, Phuong, Hoang Vu Mai, additional, Hang, Nguyen Le Khanh, additional, Mai, Le Quynh, additional, Soda, Kosuke, additional, Yamaoka, Masaoki, additional, Poetranto, Emmanuel Djoko, additional, Wulandari, Laksmi, additional, Hiramatsu, Hiroaki, additional, Daidoji, Tomo, additional, Kubota-Koketsu, Ritsuko, additional, Sriwilaijaroen, Nongluk, additional, Nakaya, Takaaki, additional, Okuno, Yoshinobu, additional, Takahashi, Tadanobu, additional, Suzuki, Takashi, additional, Ito, Toshihiro, additional, Hotta, Hak, additional, Yamashiro, Tetsu, additional, Hayashi, Tsukasa, additional, Morita, Kouichi, additional, Ikuta, Kazuyoshi, additional, and Suzuki, Yasuo, additional

Published
2015
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38. Detection of Chikungunya Virus Antigen by a Novel Rapid Immunochromatographic Test

Author

Okabayashi, Tamaki, primary, Sasaki, Tadahiro, additional, Masrinoul, Promsin, additional, Chantawat, Nantarat, additional, Yoksan, Sutee, additional, Nitatpattana, Narong, additional, Chusri, Sarunyou, additional, Morales Vargas, Ronald E., additional, Grandadam, Marc, additional, Brey, Paul T., additional, Soegijanto, Soegeng, additional, Mulyantno, Kris Cahyo, additional, Churrotin, Siti, additional, Kotaki, Tomohiro, additional, Faye, Oumar, additional, Faye, Ousmane, additional, Sow, Abdourahmane, additional, Sall, Amadou Alpha, additional, Puiprom, Orapim, additional, Chaichana, Panjaporn, additional, Kurosu, Takeshi, additional, Kato, Seiji, additional, Kosaka, Mieko, additional, Ramasoota, Pongrama, additional, and Ikuta, Kazuyoshi, additional

Published
2015
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40. A Highly Conserved Region Between Amino Acids 221 and 266 of Dengue Virus Non-Structural Protein 1 is a Major Epitope Region in Infected Patients

Author

Omokoko, Magot Diata, primary, Pambudi, Sabar, additional, Hirai, Itaru, additional, Yamashita, Akifumi, additional, Sasaki, Tadahiro, additional, Ramasoota, Pongrama, additional, Kurosu, Takeshi, additional, Phanthanawiboon, Supranee, additional, Ikuta, Kazuyoshi, additional, Setthapramote, Chayanee, additional, Kuhara, Motoki, additional, and Masrinoul, Promsin, additional

Published
2014
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46. Emerging Antigenic Variants at the Antigenic Site Sb in Pandemic A(H1N1)2009 Influenza Virus in Japan Detected by a Human Monoclonal Antibody

Author

Yasugi, Mayo, primary, Kubota-Koketsu, Ritsuko, additional, Yamashita, Akifumi, additional, Kawashita, Norihito, additional, Du, Anariwa, additional, Misaki, Ryo, additional, Kuhara, Motoki, additional, Boonsathorn, Naphatsawan, additional, Fujiyama, Kazuhito, additional, Okuno, Yoshinobu, additional, Nakaya, Takaaki, additional, and Ikuta, Kazuyoshi, additional

Published
2013
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48. Human Monoclonal Antibodies Broadly Neutralizing against Influenza B Virus

Author

Yasugi, Mayo, primary, Kubota-Koketsu, Ritsuko, additional, Yamashita, Akifumi, additional, Kawashita, Norihito, additional, Du, Anariwa, additional, Sasaki, Tadahiro, additional, Nishimura, Mitsuhiro, additional, Misaki, Ryo, additional, Kuhara, Motoki, additional, Boonsathorn, Naphatsawan, additional, Fujiyama, Kazuhito, additional, Okuno, Yoshinobu, additional, Nakaya, Takaaki, additional, and Ikuta, Kazuyoshi, additional

Published
2013
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