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Volume 61, Issue 1
Displaying 1-12 of 12 articles from this issue
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Reviews
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Kimihito ITO2011 Volume 61 Issue 1 Pages 3-14
Published: June 25, 2011
Released on J-STAGE: March 20, 2012
JOURNAL FREE ACCESSHuman influenza viruses mutate from time to time, causing annual epidemics worldwide. The strong immune pressure in the human population selects a new variant every year, and the antigenic change is one of the primary reasons why vaccination is not a perfect measure to control seasonal influenza. Thus prediction of antigenic change of influenza A virus has been one of the major public health goals. In this review bioinformatics technologies that have been developed to achieve this goal were summarized.View full abstractDownload PDF (1773K) -
Masaya SUGIYAMA, Masashi MIZOKAMI2011 Volume 61 Issue 1 Pages 15-24
Published: June 25, 2011
Released on J-STAGE: March 20, 2012
JOURNAL FREE ACCESSHBased on the data and technology generated in previous international projects, such as the Human Genome Project and the HapMap, for the building of the common patterns of genetic variation in humans, a genome-wide association study (GWAS) to HCV infection was conducted to reveal genetic effects against treatment response or the induction of side effects. Single nucleotide polymorphisms (SNPs) associated with response to pegylated-interferon (PEG-IFN) and ribavirin (RBV) therapy were determined around IL-28B in chromosome 19, and the strong association was also observed in spontaneous viral clearance regardless of population. These data imply that an important interaction between HCV infection and IL-28B is critical for viral persistence or clearance. PEG-IFN and RBV therapy is associated with a range of treatment-limiting adverse effects. One of the frequent side effects induced by the combination therapy is haemolytic anaemia. The severe anaemia requires the reduction of the RBV dose, which could lead to treatment failure. Genetic variants around inosine triphosphatase gene (ITPA) were associated with heamolytic anaemia. Interestingly, the significant SNPs observed in Europe and the United States were not strongly associated with Japanese population although all significant SNPs were located around ITPA gene, suggesting that SNPs typing using individual population are required for the collection of precise data. These significant SNPs would be useful for prediction prior to treatment for individualized medicine.View full abstractDownload PDF (1861K) -
Akio KANAI2011 Volume 61 Issue 1 Pages 25-34
Published: June 25, 2011
Released on J-STAGE: March 20, 2012
JOURNAL FREE ACCESSMany reports have been accumulated describing not a few microRNAs (miRNAs) in eukaryotes target viral genomes, whereas a number of viruses also encode miRNA genes. These small RNAs play important roles on viral infection and their replication. In germ cells, another small RNA, piRNA is reported to repress endogenous transposons. Furthermore, CRISPR RNA target virus/phage genomes in both archaea and bacteria. Therefore, small RNA is deeply involved in a broad range of biological defense systems. This system may be applied not only to control replication of viruses or phages but also provide implication on regulating the growth of microorganisms including pathogenic bacteria.View full abstractDownload PDF (974K) -
Hirotaka ODE2011 Volume 61 Issue 1 Pages 35-48
Published: June 25, 2011
Released on J-STAGE: March 20, 2012
JOURNAL FREE ACCESSMore than 20 drugs have been available for anti-HIV-1 treatment in Japan. Combination therapy with these drugs dramatically decreases in morbidity and mortality of AIDS. However, due to high mutation rate of HIV-1, treatment with ineffective drugs toward patients infected with HIV-1 causes accumulation of mutations in the virus, and emergence of drug resistant viruses. Thus, to achieve appropriate application of the drugs toward the respective patients living with HIV-1, methods for predicting the level of drug-resistance using viral sequence information has been developed on the basis of bioinformatics. Furthermore, ultra-deep sequencing by next-generation sequencer whose data analysis is also based on bioinformatics, or in silico structural modeling have been achieved to understand drug resistant mechanisms. In this review, I overview the bioinformatics studies about drug resistance against anti-HIV-1 drugs.View full abstractDownload PDF (1109K) -
Masaru YOKOYAMA2011 Volume 61 Issue 1 Pages 49-58
Published: June 25, 2011
Released on J-STAGE: March 20, 2012
JOURNAL FREE ACCESSThe third variable region (V3) of the human immunodeficiency virus type 1 (HIV-1) envelope gp120 subunit participates in determination of viral infection co-receptor tropism and host humoral immune responses. Positive charge of the V3 plays a key role in determining viral co-receptor tropism. In our previous papers, we showed a key role of the V3's net positive charge in the immunological escape and co-receptor tropism evolution in vivo. On the other hand, the several papers suggested that trimeric gp120s are protected from immune system by occlusion on the oligomer, by mutational variation, by carbohydrate masking and by conformational masking. If we can reveal the mechanism of neutralization escape, we expect that we will regulate the neutralization of HIV-1. In this review, we will overview the structural mechanism of neutralization escape of HIV-1 gp120 examined by computational science. The computational sciences for virology can provide more valuable information in combination with genomic and experimental science.View full abstractDownload PDF (4350K)
Special Issue: New Approach of HIV Research̶Symposium of 58th Annual Meeting
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Tatsuyoshi KAWAMURA2011 Volume 61 Issue 1 Pages 59-66
Published: June 25, 2011
Released on J-STAGE: March 20, 2012
JOURNAL FREE ACCESSSexual transmission of HIV is the most common mode of infection in the global HIV epidemic. In the absence of an effective vaccine, there is an urgent need for additional strategies to prevent new HIV infections. An emerging body of evidence now indicates that Langerhans cells (LC) are initial cellular targets in the sexual transmission of HIV, and CD4- and CCR5-mediated infection of LC plays a crucial role in virus dissemination. I focus on the recent advances regarding the cellular events that may occur during heterosexual transmission of HIV.View full abstractDownload PDF (2506K) -
Yasumasa IWATANI2011 Volume 61 Issue 1 Pages 67-72
Published: June 25, 2011
Released on J-STAGE: March 20, 2012
JOURNAL FREE ACCESSHuman cells developed the defense systems against retrovirus infections during the evolutions. These systems include retroviral restrictions by DNA cytidine deaminases of APOBEC3 family (A, B, C, DE, F, G, and H), which are potent factors to block the viral replication by blocking reverse transcription and/or integration and by hypermutating viral cDNA. In case of HIV-1, the viral protein, Vif abrogates the APOBEC3F/G function through specific machinery of ubiquitination and proteasomal degradation. Without Vif, APOBEC3F/G are incorporated into virus particles and block reverse transcription and/or integration in a newly infected cell. Recent advances in our understanding about biochemical and structure-biological characteristics of the enzymes provide new insights to reveal more detailed molecular mechanisms for anti-retroviral activity by APOBEC3 family. Here I briefly review how APOBEC3 proteins block retrovirus replications, focusing on APOBEC3G.View full abstractDownload PDF (1490K) -
Takao MASUDA2011 Volume 61 Issue 1 Pages 73-80
Published: June 25, 2011
Released on J-STAGE: March 20, 2012
JOURNAL FREE ACCESSReverse transcription of retroviral RNA into double stranded DNA is a characteristic feature of rertoviruses including human immunodeficiency virus type I (HIV-1). There has been accumulating evidence for the involvement of retroviral integrase (IN) in the reverse transcription of viral RNA. Here, we summarized recent our studies demonstrating direct functional roles of IN and its binding partner of host factor, Gemin2 in the reverse transcription. We established new in vitro cell-free assay to mimic natural reverse transcription and found that HIV-1 IN and host factor, Gemin2 synergistically stimulate reverse transcriptase (RT) activity. Analysis of intracellular stability and multimer formation of IN suggest that that high-ordered structures, especially tetramer formation of IN is critical for the function. In addition, Gemin2 might have a role to keep the higher-order structure of IN. Thus, we provide new aspects of reverse transcription of HIV-1through IN and host factors in addition to RT.View full abstractDownload PDF (1699K) -
Takashi OKAMOTO2011 Volume 61 Issue 1 Pages 81-90
Published: June 25, 2011
Released on J-STAGE: March 20, 2012
JOURNAL FREE ACCESSThe RNA genome of retroviruses including human immunodeficiency virus type 1 (HIV-1) will be converted into DNA, called "propvirus". This proviral DNA will be integrated into host cell genome and behave like host genes. Since the step at which the viral RNA genome is converted into DNA will not allow any increase of viral genetic information because of the presence of RNaseH activity inherent to the reverse transcriptase and is responsible for the degradation of viral RNA in forming the DNA:RNA hybrid as the intermediate molecule for this conversion. However, during transcription from proviral DNA into viral RNA, hundreds and even thousands of mRNA encoding viral information will be synthesized by the action of host cellular RNA polymerase II, thus producing a large amount of progeny viral particles after translation and assembly. HIV is unique in that it contains virus-specific transcriptional activator called TatView full abstractDownload PDF (1771K) -
Jun-ichi SAKURAGI2011 Volume 61 Issue 1 Pages 91-98
Published: June 25, 2011
Released on J-STAGE: March 20, 2012
JOURNAL FREE ACCESSIn general, the retrovirus particles become infectious on post-budding with cleavages of structural protein Gag by viral protease. Protease defective mutants bud particles normally, but the particles are non-infectious and called donuts-like particle because of their morphology. The viral genomes inside the donuts-like particles form very fragile dimer, which are far different from those in wild-type particles. The ordered particle maturation process is essential for infectivity of virus, but its mechanism largely remains unclear. We have constructed HIV-1 Gag cleavage site mutants to enable the steady state observation of virion maturation steps, and precisely study Gag processing, RNA dimerization, virion morphology and infectivity. As results, we found that these process progressed synchronously, but each transition point did not coincide completely. The mutual relationship between viral protein and RNA maturation is discussed for a further understanding of the retroviral life cycle.View full abstractDownload PDF (2141K)
SUGIURA Memorial Incentive Award for Young Virologist, The Japanese Society for Virology, 2010
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Hideki TANI2011 Volume 61 Issue 1 Pages 99-108
Published: June 25, 2011
Released on J-STAGE: March 20, 2012
JOURNAL FREE ACCESSVirus is identified as one of the obligate intracellular parasites, which only amplify in cells of specific living things. Viral vectors, which are developed by utilizing these properties, are available in the various fields such as basic research of medical biology or application of gene therapy. Our research group has studied development of viral vectors using properties of baculovirus or vesicular stomatitis virus (VSV). Due to the development of new baculoviral vectors for mammalian cells, it is possible to be more efficient transduction of foreign gene in mammalian cells and animals. Furthermore, pseudotype or recombinant VSV possessing the envelope proteins of hepatitis C virus, Japanese encephalitis virus or baculovirus were constructed, and characteristics of the envelope proteins or entry mechanisms of these viruses were analyzed.View full abstractDownload PDF (3414K) -
Shutoku MATSUYAMA2011 Volume 61 Issue 1 Pages 109-116
Published: June 25, 2011
Released on J-STAGE: March 20, 2012
JOURNAL FREE ACCESSPrevious studies have demonstrated that the SARS-CoV S protein requires proteolytic cleavage by elastase, cathepsin or TMPRSS2 for S-mediated cell-cell or virus-cell membrane fusion. Activation of viral glycoprotein (GP) by protease also has been reported for influenza virus. The most distinctive difference between influenza virus and SARS-CoV is the stage during virus replication in which viral glycoproteins are cleaved by proteases. In influenza virus, the protease makes a simple cut in the GP during maturation. In contrast, SARS-CoV S protein is cleaved by the protease following receptor-induced conformational changes. The protease cleavage site in S protein is thought to be exposed only after receptor binding. In support of this model, we reported that the S protein of mouse hepatitis virus type 2 (MHV-2), which is highly similar to the S protein of SARS-CoV, requires two-step conformational changes mediated by sequential receptor binding and proteolysis to be activated for membrane fusion. Such a mechanism allows for tight temporal control over fusion by protecting the activating cleavage site from premature proteolysis yet allowing efficient cleavage upon binding to the receptor on target cells.View full abstractDownload PDF (763K)
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