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Volume 62, Issue 1
Displaying 1-14 of 14 articles from this issue
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Reviews
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Takasuke FUKUHARA, Yoshiharu MATSUURA2012 Volume 62 Issue 1 Pages 1-8
Published: June 25, 2012
Released on J-STAGE: May 09, 2013
JOURNAL FREE ACCESSHepatitis C virus (HCV) exhibits a narrow host range and a specific tissue tropism. Studies on HCV life cycle have been progressed by the developments of in vitro replication and infection systems and an HCV laboratory strain (HCVcc) capable of propagating in human hepatoma cell line, Huh7 cells. Mice expressing four human entry receptor candidates for HCV permit entry of HCVcc, therefore tissue tropism of HCV was believed to be rely on the expression of the entry receptors. However, HCV infection is often associated with extra-hepatic manifestations and the determinants for cell tropism of HCV remain elusive. Recently, we have shown that several nonhepatic cell lines permit HCV-RNA replication through an expression of a liver-specific microRNA, miR-122, upon infection with HCVcc, while no infectious particle was produced. In the nonhepatic cells, only small numbers of lipid droplets and low levels of VLDL-associated proteins were observed in compared with Huh7 cells, suggesting that expression of miR-122 and functional lipid metabolism participates in the replication and assembly of HCVcc, respectively. In this review, we would like to discuss about involvement of miR-122 and functional lipid metabolism in the determination of HCV cell tropism.View full abstractDownload PDF (717K) -
Makoto YAMAGISHI, Toshiki WATANABE2012 Volume 62 Issue 1 Pages 9-18
Published: June 25, 2012
Released on J-STAGE: May 09, 2013
JOURNAL FREE ACCESSAlthough human T cell leukemia virus type I (HTLV-I) is undoubtedly involved in the immortalization and leukemogenesis of infected cells, mechanistic underpinnings of its molecular pathophysiology in long latent period of Adult T-cell leukemia (ATL) remain to be elucidated. One of the most significant recent advances in biomedical research has been the discovery of small noncoding RNAs designated microRNA (miRNA), which affect the field of virology including HTLV-1 research. Mounting evidence indicates that viruses use these miRNAs to manipulate both cellular and viral gene expression. Viral infection also can exert a profound impact on the cellular miRNA expression profile. Some studies have demonstrated that some deregulations of miRNA are involved in the pathogenesis of HTLV-1. Furthermore, global analyses of ATL patient samples have provided a conceptual progress that Polycomb family induces miR-31 silencing, resulting in overexpression of NF-κB inducing kinase (NIK) following NF-κB activation. Given that miRNAs act as pleiotropic molecules essential in all cellular events, deregulation of miRNA signature caused by HTLV-1 infection strongly involves the imbalance of molecular network of lymphocytes. Recognition and understanding of the widespread molecular applicability of miRNAs will increasingly have much effect on the development of novel strategies to treat the HTLV-1-associated diseases. Here we discuss our current knowledge of viral miRNAs and virally influenced cellular miRNAs and their relationship to ATL.View full abstractDownload PDF (1412K) -
Hanako SHIMURA, Chikara MASUTA2012 Volume 62 Issue 1 Pages 19-26
Published: June 25, 2012
Released on J-STAGE: May 09, 2013
JOURNAL FREE ACCESSRNA silencing plays an important role in plant resistance against viruses. As a counter-defense against RNA silencing, plant viruses have evolved RNA silencing suppressors (RSSs). RNA silencing is likely to play a major role in disease development. For example, RSSs have been found to disturb the gene expression controlled by miRNAs in plant tissue and organ development, resulting in plant malformation. Mosaic symptoms, which are typical in virus-infected plants, are actually a consequence of local arms race between host RNA silencing and viral RSSs. In addition, recent studies revealed that viral siRNAs could induce RNA silencing even against a certain host gene and thus a disease symptom through a complementary (homologous) sequence coincidentally found between virus and host gene. RNA silencing is the principal mediator of viral pathogenicity and disease induction and therefore should be exploited as a powerful tool for engineering virus resistance in plants as well as in animals.View full abstractDownload PDF (3433K) -
Masaaki MIYAZAWA2012 Volume 62 Issue 1 Pages 27-38
Published: June 25, 2012
Released on J-STAGE: May 09, 2013
JOURNAL FREE ACCESSRecent in vivo findings clearly indicate that mammalian cytidine deaminase APOBEC3 can function as a physiological restriction factor to retrotransposons and infectious retroviruses. However, some retroviruses, including primate lentiviruses, have evolved to counter their natural host's APOBEC3. To survive this arms race, primates seem to have acquired multiple copies of APOBEC3 genes. Surprisingly, however, during the process of the diversification of rodent species, as well as the human race, some ancestral individuals acquired genetic variants that reduced the protein levels of APOBEC3 expression, and these variants currently show unexpectedly wide geographic distributions. These data suggest that in the absence of a heavy burden of infectious retroviruses, high-level expression of APOBEC3 cytidine deaminase might be costly to the integrity of the host genome.View full abstractDownload PDF (1581K)
Special Issue 1:Plenary session in ICV2011/JSV59
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Shizuo AKIRA, Tatsuya SAITOH, Taro KAWAI2012 Volume 62 Issue 1 Pages 39-46
Published: June 25, 2012
Released on J-STAGE: May 09, 2013
JOURNAL FREE ACCESSThe innate immune system detects pathogen-derived nucleic acids (DNA and RNA) and induces type I interferon (IFN) and other cytokines, resulting in the host defense against pathogen. We identified interferon-inducible tripartite-motif (TRIM) 56 as a regulator of double-stranded DNA-mediated type I interferon induction. TRIM56 interacted with STING and targeted it for lysine 63-linked ubiquitination. This modification induced STING dimerization, which was a prerequisite for recruitment of the antiviral kinase TBK1 and subsequent induction of IFN-β. Taken together, these results show that TRIM56 is an interferon-inducible E3 ubiquitin ligase that modulates STING to confer double-stranded DNA-mediated innate immune responses.
It is well known that Toll-like receptor 7 (TLR7) and TLR9 sense viral nucleic acids and induce production of type I interferon (IFN) by plasmacytoid dendritic cells (pDCs) to protect the host from virus infection. We showed that the IFN-inducible antiviral protein Viperin promoted TLR7- and TLR9-mediated production of type I IFN by pDCs. Viperin expression was potently induced after TLR7 or TLR9 stimulation and Viperin localized to the cytoplasmic lipid-enriched compartments, lipid bodies, in pDCs. Viperin interacted with the signal mediators IRAK1 and TRAF6 to recruit them to the lipid bodies and facilitated K63-linked ubiquitination of IRAK1 to induce the nuclear translocation of transcription factor IRF7. Thus, besides direct inhibition of viral replication, this finding reveals that Viperin mediates its antiviral function via the regulation of the TLR7 and TLR9-IRAK1 signaling axis in pDCs.View full abstractDownload PDF (696K) -
Keizo TOMONAGA2012 Volume 62 Issue 1 Pages 47-56
Published: June 25, 2012
Released on J-STAGE: May 09, 2013
JOURNAL FREE ACCESSThe origin of virus-like organisms probably dates back to the earliest forms of cellular life. Such a long coexistence between viruses and ourselves suggests that viruses may have crucially influenced the evolution of our species and vice versa. Sequences derived from retroviruses and retrotransposons have been shown to make up a substantial part of the human genome, suggesting a direct role of virus infection as a source of new genetic information and genomic innovation of the host species. Until very recently, retroviruses were the only viruses known to generate such endogenous copies in vertebrate genomes. However, we and others have reported recently that non-retroviral RNA viruses, including bornaviruses and filoviruses, have been endogenized repeatedly during mammalian evolution. These endogenous elements of RNA viruses not only provide evidence of ancient viral infections in each animal species but also offer novel paradigms for the interaction between RNA viruses and their hosts. Based on the presentation of the plenary lecture at the XV International Congress of Virology 2011, I will review here our recent findings regarding the generation and functions of endogenous bornavirus-like N elements in mammalian genomes, in order to reveal the unknown dynamics of RNA viruses in eukaryotic cells, and also discuss the evolutionary interaction between RNA viruses and hosts.View full abstractDownload PDF (1269K)
Special Issue 2:Current topics in vaccine in Japan
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Hiroyuki SHIMIZU2012 Volume 62 Issue 1 Pages 57-66
Published: June 25, 2012
Released on J-STAGE: May 09, 2013
JOURNAL FREE ACCESSTo avoid the risk of vaccine-associated paralytic poliomyelitis (VAPP) and polio outbreaks due to circulating vaccine-derived polioviruses, an inactivated poliovirus vaccine (IPV) was introduced for routine immunization in a number of countries with a low risk of polio outbreaks. Currently, production and marketing of a standalone conventional IPV and two diphtheria-pertussis-tetanus-IPV (Sabin-derived IPV; sIPV) products have been submitted, and it is expected that the IPV products will be introduced in Japan in the autumn of 2012. At the same time, a decline in the OPV immunization rate became apparent in Japan due to serious public concerns about a remaining risk of VAPP and introduction of IPV in the near future. Therefore, the recent development of polio immunity gaps should be carefully monitored, and surveillance of suspected polio cases and laboratory diagnosis of polioviruses have to be intensified for the transition period from OPV to IPV in Japan. The development of sIPV is one of the most realistic options to introduce affordable IPV to developing countries. In this regard, further clinical studies on its efficacy, safety, and interchangeability of sIPV will be needed after the introduction of the sIPV products, which will be licensed in Japan for the first time in the world.View full abstractDownload PDF (731K) -
Masashi MIZOKAMI, Masaya SUGIYAMA2012 Volume 62 Issue 1 Pages 67-78
Published: June 25, 2012
Released on J-STAGE: May 09, 2013
JOURNAL FREE ACCESSHepatitis B virus (HBV) prevention program in Japan is considered one of the most successful and effective public anti-counter programs to HBV infection. However, almost all of population under twenty-five years is extremely susceptibility for HBV infection. HBV genotype A, which was not in Japan and has been from western countries, is increasing in chronic hepatitis B patients in Japan as a consequence of acute hepatitis B spreading in the younger generation through promiscuous sexual transmitted infection and the characteristics of HBV genotype A is a prolonged high HBVDNA viremia compared with other HBV genotypes. These data have strongly indicated that the main transmission route of HBV in Japan has been changed to a horizontal infection with sexual transmitted disease from perinatal transmission from HBsAg positive mothers. Although the HBV vaccine has tipped the balance in our favor, newly issues of HBV vaccine has been arisen such as vaccine escape mutant, efficacy and potency for the prevention of HBV infection, especially different HBV genotypes, HBV reactivation on the patients with HBsAg negative and anti-HBs antibody positive under systemic chemotherapy, and universal vaccination or selective vaccination and so on.
We discussed on these problems and would be also developed to HBV vaccine.View full abstractDownload PDF (1480K) -
Kei KAWANA2012 Volume 62 Issue 1 Pages 79-86
Published: June 25, 2012
Released on J-STAGE: May 09, 2013
JOURNAL FREE ACCESSHuman papillomavirus causes viral-dependent cancers, including cervical, anal, vulvar, penile, vaginal, and oropharyngeal, and condyloma acuminata. In the last decade, HPV prophylactic vaccine has been developed and spread worldwide after many large-scale clinical studies. These studies demonstrate significant clinical efficacy for prevention of HPV16/18/6/11-related diseases. In particular, prevention of cervical cancer should be the most important role in the world. In Japan, incidence of cervical cancer does not increase, but the peak of age of the patients at 2005 is 25-45 years old and became 20 years younger than that at 1985. The current two HPV vaccines can prevent the infection of HPV16/18 among high-risk HPVs and will provide a significant impact especially on young-age onset cervical cancer. Furthermore, quadrivalent HPV vaccine, Gardasil, has shown population impact that is decrease of patients with condyloma acuminate in several countries. The clinical efficacy seems to be convincing. Here HPV vaccine will be reviewed based on the literatures.View full abstractDownload PDF (1230K) -
Koki TANIGUCHI2012 Volume 62 Issue 1 Pages 87-96
Published: June 25, 2012
Released on J-STAGE: May 09, 2013
JOURNAL FREE ACCESSSince the presentation of the clinical trial reports showing the excellent efficacy and safety of the two human rotavirus vaccines (Rotarix and RotaTeq), the human rotavirus vaccines have received worldwide attention. The two vaccines have been approved in more than 100 countries, and were included in routine immunization schedule in about 30 countries. The effectiveness of the two vaccines exceeded our expectations, and severe rotavirus gastroenteritis cases have been greatly reduced. Also in Japan, administration of Rotarix started just last November, and RotaTeq will be also started soon. On this occasion, composition, characteristics, and effectiveness of these vaccines are described, and some points relating to the vaccination such as intussusception, cross protection, shedding and so on are also discussed.View full abstractDownload PDF (759K)
Topics:Two Different Receptors for Wild Type Measles Virus
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Masato TASHIRO2012 Volume 62 Issue 1 Pages 97-102
Published: June 25, 2012
Released on J-STAGE: May 09, 2013
JOURNAL FREE ACCESS
SUGIURA Memorial Incentive Award for Young Virologist, The Japanese Society for Virology, 2011
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Takayuki ABE2012 Volume 62 Issue 1 Pages 103-112
Published: June 25, 2012
Released on J-STAGE: May 09, 2013
JOURNAL FREE ACCESSThe baculovirus Autographa californica multiple nuclear polyhedrosis virus (AcMNPV) has been widely used not only to achieve a high level of foreign gene expression in insect cells but also for efficient gene transduction into mammalian cells without any replication. In addition to the efficient gene delivery, baculovirus has been shown to induce host innate immune responses in various mammalian cells and in mice. The baculovirus has abundant CpG motifs in the viral genome and is capable of inducing pro-inflammatory cytokines and interferons (IFNs) through Toll-like receptor (TLR)-dependent and -independent signaling pathways in a cell-type-specific manner. The cytoplasmic helicase proteins RIG-I (retinoic-acid-inducible protein I) and MDA5 (melanoma-differentiation-associated gene 5) have been identified as viral dsRNA detectors and the adaptor IPS-1 (IFN-β promoter stimulator-1) interacts with RIG-I and MDA5 to facilitate type-I IFN production mediated interferon regulatory factor 3 (IRF3) and 7 (IRF7). These helicases and IPS-1, however, were not essential for the type-I IFN and inflammatory cytokine responses to baculovirus. The baculovirus also has a strong adjuvant activity, and recombinant baculoviruses encoding neutralization epitopes elicit protective immunity in mice. This review deals with the current status of our knowledge of the induction of host innate immune responses by baculovirus and discusses the future prospects for baculovirus vectors.View full abstractDownload PDF (2803K) -
Yorifumi SATOU2012 Volume 62 Issue 1 Pages 113-120
Published: June 25, 2012
Released on J-STAGE: May 09, 2013
JOURNAL FREE ACCESSHTLV-1 is a retrovirus associated with human diseases, such as ATL or HAM/TSP. More than thirty years have passed since HTLV-1 was discovered, but the precise mechanism of HTLV-1 pathogenesis still remains elusive. HTLV-1 bZIP factor (HBZ) was reported ten years ago as a viral gene encoded in the minus strand of HTLV-1. We have elucidated that HBZ is constitutively detectable in all ATL cells examined whereas tax expression is frequently lost. Furthermore, we and other researchers have reported that HBZ expression contributes to the proliferation of infected cells. We have shown that HBZ has the potential to transform T cells in vivo by analyzing HBZ-transgenic mice. Further investigations will uncover a more detailed role of HBZ in HTLV-1 pathogenesis. This paradigm shift of HTLV-1 research should provide novel target in prevention or treatment of HTLV-1-related human diseases.View full abstractDownload PDF (1158K) -
Yorihiro NISHIMURA2012 Volume 62 Issue 1 Pages 121-128
Published: June 25, 2012
Released on J-STAGE: May 09, 2013
JOURNAL FREE ACCESSIdentification of a specific viral receptor is important for understanding the virus infection mechanism. I identified P-selectin glycoprotein ligand-1 (PSGL-1) as one of the functional receptors for enterovirus 71 (EV71), a pathogen that causes hand, foot, and mouth disease. PSGL-1, which belongs to the sialomucin family, is a transmembrane protein mainly expressed on leukocytes. Tyrosine sulfation in the N-terminal region of PSGL-1 is critical for PSGL-1's capacity to bind EV71. The identification of EV71 receptors provides important mechanistic information about viral entry into cells and helps us understand viral pathogenesis and develop new anti-viral strategies.View full abstractDownload PDF (1152K)
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