Uirusu
Online ISSN : 1884-3433
Print ISSN : 0042-6857
ISSN-L : 0042-6857
Volume 63, Issue 2
Displaying 1-10 of 10 articles from this issue
Reviews
  • Tsukasa SEYA, Hiroyuki OSHIUMI, Misako MATSUMOTO
    2013 Volume 63 Issue 2 Pages 135-142
    Published: December 25, 2013
    Released on J-STAGE: October 31, 2014
    JOURNAL FREE ACCESS
    Viruses infect host circumventing the host immune system; a variety of strategies for establishment of viral infection have been found in a virus-specific fashion. Infection with RNA viruses allows host dendritic cells to present antigens and a typical pattern (PAMP) of virus products, including the RNA genomes and replication intermediates such as double-stranded RNA (dsRNA), which induce antiviral effectors: type I interferons (IFN), cytokines, NK cell activation, Th1 polarization, CD8 T cell proliferation, etc. These findings revealed that RNA-sensing innate system closely links to a trigger of cellular immunity. This process unequivocally involves the maturation of antigen-presenting dendritic cell (mDC), and virus products frequently block this step. According to these findings, mDC have to sense non-self RNA to establish antiviral immunity without spoiling their functions via infection, except several exceptional cases. The notion infers that the RNA recognition in cytosol of infected cells (intrinsic sensing) functions as virocidal whereas that in mDC (extrinsic sensing) differentially converges on another antiviral strategy, activation of the immune system. In this review, we focus on the potential role of hepatitis C virus (HCV) RNA in modulating the inflammatory milieu around mDCs and evoking antiviral immunity to drive specific cellular effectors against the virus.
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  • Hideki KONDO
    2013 Volume 63 Issue 2 Pages 143-154
    Published: December 25, 2013
    Released on J-STAGE: October 31, 2014
    JOURNAL FREE ACCESS
    Members of the family Rhabdoviridae (order Mononegavirales) have a broad range of hosts, including humans, livestock, fish, plants, and invertebrates. They have a nonsegmented negative-sense RNA as the genome. Orchid fleck virus (OFV) is distributed world-wide on several orchid plants and transmitted by the false spider mite, Brevipalpus californicus. Based on its virions morphology and cytopathic effects in the infected cells, OFV was tentatively placed as unassigned plant rhabdoviruses in the sixth ICTV Report. However, the molecular studies reveled that OFV has a unique two-segmented negative-sense RNA genome that resembles monopartite genomes of plant nucleorhabdoviruses. In this review, we describe the current knowledge on the genome structure and gene expression strategy of OFV, the possible mechanism of nuclear viroplasm formation, and the taxonomical consideration of the virus as well.
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  • Saki KONDO, Aya MAEKAWA, Izumu SAITO, Yumi KANEGAE
    2013 Volume 63 Issue 2 Pages 155-164
    Published: December 25, 2013
    Released on J-STAGE: October 31, 2014
    JOURNAL FREE ACCESS
    First-generation adenovirus vectors (FG-AdVs) are widely used because transduction efficiency of the vectors is very high. However, severe immune responses especially to the liver have been a serious problem of this vector. We succeeded to identify a viral protein that cause the immune responses and reported ''low-inflammatory AdVs'' that mostly solve this problem. However, to develop the ultimate form of this vector, it is necessary to remove virus-associated RNA (VA RNA) genes from the AdV vector genome. VA RNAs are transcribed by polymerase III; they are not essential for viral growth but have important roles to make appropriate circumstances for this virus. Large amount of VA RNAs are required in the late phase to support viral growth. Hence it is difficult to establish 293 cell lines that can support replication of AdVs lacking VA RNA genes (VA-deleted AdVs) supplying sufficient amount of VA RNA in trans. Recently we have developed a method for efficient production of VA-deleted AdVs and succeeded to obtain a high titer of VA-deleted AdVs. Then we construct VA-deleted AdVs expressing shRNA that knockdown the replication of hepatitis C virus (HCV). In fact, VA-deleted AdVs expressing these shRNAs suppressed HCV replication more effectively than conventional FG-AdV. Therefore, we showed that VA RNAs expressed from FG-AdVs probably compete with shRNA in the maturation pathway and reduce the effect of shRNAs. We think that VA-deleted AdV may substitute for current FG-AdVs and become a standard AdV.
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Special Issue: Retrovirology
  • Jun-ichiro YASUNAGA, Masao MATSUOKA
    2013 Volume 63 Issue 2 Pages 165-174
    Published: December 25, 2013
    Released on J-STAGE: October 31, 2014
    JOURNAL FREE ACCESS
    Human T-cell leukemia virus type 1 (HTLV-1) belongs to Delta Retorviridae, and induces a malignancy of CD4+CD25+ T-cells, adult T-cell leukemia (ATL), and several chronic inflammatory diseases, such as HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) and HTLV-1 uveitis. A nationwide survey of HTLV-1-infected subjects, which was recently conducted by Japanese government, revealed that the numbers of HTLV-1 carriers and patients with HTLV-1-associated diseases have not decreased much over the last two decades in Japan. In contrast, novel findings on HTLV-1 dynamics in vivo and molecular mechanisms of its pathogenesis are accumulating by detailed analysis of newly identified viral and cellular factors, novel technologies such as next-generation sequencing, and appropriate animal models for HTLV-1 research. In this review, we summarize the recent progress of HTLV-1 research.
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  • Jun-ichi SAKURAGI
    2013 Volume 63 Issue 2 Pages 175-186
    Published: December 25, 2013
    Released on J-STAGE: October 31, 2014
    JOURNAL FREE ACCESS
    It has been 30 years passed since the discovery of HIVs as the agents of AIDS. During the period, many energetic research works about this gigantic menace have been performed globally and many outcomes have been applied to intercept the epidemic. Because of a brilliant progress of the therapeutic strategy, it is said that AIDS is no longer the deadly disease, but one of the mere chronic disease nowadays. On the other hand, giving an eye to the virus itself, many dark gaps are found in a superficially good-looking story of the viral replication. Thus, we are still far from fundamental understanding of the virus. In this review, I especially pick up the viral genome RNA as a central player of the story and give an introduction about various steps of viral replication. With several recent reports, I will exposit well-known and/or unclear events around virus.
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  • Shingo KITAMURA, Yasumasa IWATANI
    2013 Volume 63 Issue 2 Pages 187-198
    Published: December 25, 2013
    Released on J-STAGE: October 31, 2014
    JOURNAL FREE ACCESS
    HIV has several accessory proteins (Vif, Vpu, Vpr, Vpx, and Nef) along with structural /enzymatic (Gag, Pol, and Env) and gene-expression regulatory proteins (Tat and Rev) essential for viral replication. The accessory proteins are neither required in some kinds of cells and nor all conserved between HIV-1 and HIV-2. For these reasons, their functional roles and mechanisms had been unclear. However, since a finding of Vif’s neutralizing function against host restriction factor APOBEC3G, it has been elucidated that the accessory proteins play critical roles to antagonize host intrinsic antiviral activity. So far, in addition to Vif-APOBEC3, Vpu-BST-2/Tetherin and Vpx-SAMHD1 have been identified as such examples. Here, we summarize the biological functions and features on HIV accessory proteins in terms of antagonizing factors against the host antiviral factors.
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  • Tomohiko KOIBUCHI
    2013 Volume 63 Issue 2 Pages 199-208
    Published: December 25, 2013
    Released on J-STAGE: October 31, 2014
    JOURNAL FREE ACCESS
    Anti-HIV drugs are fall into the following 5 categories: nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), integrase strand transfer inhibitors (INSTIs), and C-C chemokine receptor type 5 (CCR5) inhibitors. An appropriate combination of anti-HIV drugs, which is called ART (anti-retroviral therapy), can suppress HIV replication for prolonged periods. Since many anti-HIV drugs with relatively few side effects as well as high-potency have been developed recently, early initiation of ART is recommended regardless of the patients’ CD4+ T-cell counts. However, ART does not lead to eradication or cure of HIV because of latent infection. Interruption of ART leads to a rapid rebound of viremia, necessitating life-long treatment. Thus, strategies to eradicate HIV from latently infected cells are urgently needed.
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  • Hayato MURAKOSHI, Masafumi TAKIGUCHI
    2013 Volume 63 Issue 2 Pages 209-218
    Published: December 25, 2013
    Released on J-STAGE: October 31, 2014
    JOURNAL FREE ACCESS
    IV-specific cytotoxic T lymphocytes (CTLs) play an important role in control of HIV infection. HLA class I molecules, which mediate recognition of HIV-infected cells by the CTLs, have great diversity. Some HLA class I molecules are well known to associate with HIV control. HIV escapes from the CTLs through amino acid mutations within CTL epitopes. The rapid and extensive spread of HIV escape mutants provides accumulation of the mutants at a population level, demonstrating strong evidence of HIV adaptation to HLA class I. In this review, we discuss the role of the CTLs in controlling HIV, the relationship between HLA alleles and HIV control, and the accumulation of HIV mutants selected by the CTLs at a population level.
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  • Hiroyuki YAMAMOTO
    2013 Volume 63 Issue 2 Pages 219-232
    Published: December 25, 2013
    Released on J-STAGE: October 31, 2014
    JOURNAL FREE ACCESS
    Prophylactic AIDS vaccines are required to optimally load adaptive immune responses against a virus optimally designed to impair those responses and induce persistent infection. This inevitably may necessitate atypical induction patterns that are distinct from well-balanced responses deriving from the inherent immunological framework. This review discusses how the diverse features of pathologic context-dependent T-cell (CTL/Th) and B-cell (neutralizing antibody) responses may be incorporated into vaccine-induced immunity to achieve HIV control in vivo.
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