- Volume 90, Issue 9, 2009
Volume 90, Issue 9, 2009
- Animal
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- DNA viruses
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STAT1 contributes to the maintenance of the latency III viral programme observed in Epstein–Barr virus-transformed B cells and their recognition by CD8+ T cells
The transformation of B cells by Epstein–Barr virus (EBV), into lymphoblastoid cell lines (LCLs) results in the upregulation of STAT1, a key transcription factor in the interferon signalling pathway. Although the mechanism of EBV induction of STAT1 protein expression has been intensively studied, there has been little investigation into the function of STAT1 in EBV-transformed LCLs. In this study, we have implemented a novel strategy to investigate the functional role of STAT1 through the introduction of the simian virus 5 (SV5) V-protein into LCLs by retroviral gene transfer. The V-protein is a virally evolved STAT1 inhibitor that specifically targets STAT1 for proteasomal degradation. Using this in vitro model, we have shown that major histocompatibility complex (MHC) class I and class II molecules are downregulated at the cell surface following a reduction in STAT1 protein expression. With regards to MHC class I, the impairment of the antigen processing machinery renders the cells less recognized by the host EBV-specific immunosurveillance. In addition, downregulation of STAT1 increases the expression of LMP2A and lytic cycle antigens and results in a higher proportion of cells entering the lytic cycle. These results suggest that STAT1 is involved in maintaining the latency III viral program observed in transformed B cells and regulating immunorecognition by EBV-specific T cells.
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Phosphorylation sites of Epstein–Barr virus EBNA1 regulate its function
More LessEpstein–Barr virus (EBV) is the causative agent of infectious mononucleosis and a risk factor for developing a variety of lymphomas and carcinomas. EBV nuclear antigen 1 (EBNA1) is the only viral protein found in all EBV-related malignancies. It plays a key role in establishing and maintaining the altered state of cells transformed with EBV. EBNA1 is required for a variety of functions, including gene regulation, replication and maintenance of the viral genome, but the regulation of EBNA1's functions is poorly understood. We demonstrate that phosphorylation affects the functions of EBNA1. By using electron-transfer dissociation tandem mass spectrometry, ten specific phosphorylated EBNA1 residues were identified. A mutant derivative preventing the phosphorylation of all ten phosphosites retained the unusually long half-life and the ability to translocate into the nucleus of wild-type EBNA1. This phosphorylation-deficient mutant, however, had a significantly reduced ability to activate transcription and to maintain EBV's plasmids in cells.
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Nucleotide sequence variation in the hexon gene of human adenovirus type 8 and 37 strains from epidemic keratoconjunctivitis patients in Japan
Human adenovirus type 8 (HAdV-8) and 37 (HAdV-37) cause epidemic keratoconjunctivitis (EKC) associated with community-acquired and nosocomial infections. The nucleotide sequences of the entire hexon and fiber genes of eight HAdV-8 and 26 HAdV-37 strains were analysed and the transition mutations in each gene were compared among strains. Compared with prototype strains, the hexon gene of HAdV-8 and -37 strains showed between two and seven and one and twelve variations at nine and 21 different positions, respectively. All of these, except one position in HAdV-37, were located in the conserved region 4 (C4). There were only three polymorphisms in the fiber gene of both HAdV-8 and HAdV-37, fewer than those in C4. The nucleotide sequence of HAdV-8 and -37 C4 might be readily modified during EKC epidemics.
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Virulence and pathophysiology of the Congo Basin and West African strains of monkeypox virus in non-human primates
Monkeypox virus is divided into Congo Basin and West African strains. The virulence and pathophysiology of two strains, Zr-599 (a Congo Basin monkeypox virus) and Liberia (a West African monkeypox virus), were evaluated in non-human primates. Four monkeys were infected by the subcutaneous (SC) and two by the intranasal (IN) inoculation routes for Zr-599 and Liberia at a dose of 106 p.f.u. One monkey in the Liberia/SC group was demonstrated to be co-infected with Gram-positive cocci and was excluded from analyses. Infections in three of the four Zr-599/SC monkeys and in one of the three Liberia/SC monkeys were fatal. Virus genome levels in blood in the Zr-599/SC monkeys were approximately 10 times higher than those in the Liberia/SC monkeys. Zr-599 affected respiratory, genito-urinary and gastrointestinal tract organs more severely than Liberia. Zr-599 was more virulent than Liberia and one of the factors might be the difference in organ tropism.
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Genetic dissection of naturally occurring basal core promoter mutations of hepatitis B virus reveals a silent phenotype in the overlapping X gene
More LessDuring chronic hepatitis B virus (HBV) infection, double substitution mutations in the basal core promoter (BCP) region frequently emerge that include A1762T/G1764A and the neighbouring C1766T/T1768A mutations, here termed BCP1 and BCP2, respectively. Due to a compact viral genome organization, BCP1 and BCP2 mutations result in amino acids changes in the overlapping X gene: K130M/V131I and F132Y, respectively. It has been shown that both BCP mutations lead to a modest increase in viral genome replication. However, the question of whether the alteration that occurs in the overlapping X gene might contribute to the increased viral genome replication has not been properly addressed. This study genetically separated the core promoter from the overlapping X gene using 1.3mer overlength HBV constructs and examined the impact of the X gene mutations on viral genome replication in HepG2 cells. Each BCP mutation resulted in modestly enhanced viral genome replication that occurred via augmented viral transcription. Therefore, it was concluded that these BCP mutations do not affect expression of the overlapping X gene or impair its stimulatory effect on viral genome replication.
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Transduction of vertebrate cells with Spodoptera exigua multiple nucleopolyhedrovirus F protein-pseudotyped gp64-null Autographa californica multiple nucleopolyhedrovirus
More LessBudded virions of the baculovirus Autographa californica multiple nucleopolyhedrovirus (AcMNPV) can enter a variety of non-host cells. The capacity of GP64, AcMNPV's endogenous envelope fusion protein, and SeF, the fusion protein from a gp64 − baculovirus, to mediate baculovirus entry into vertebrate cells was examined by comparing the transduction efficiencies of engineered AcMNPV variants with either of the two envelope proteins into 17 vertebrate cell lines. At an m.o.i. of 500, GP64-expressing viruses transduced all cell lines with varying efficiencies. Transduction efficiencies of SeF-pseudotyped gp64-null AcMNPV into all cell lines were lower than those of GP64-expressing viruses, and were undetectable in seven cell lines. At an m.o.i. of 50, transduction of all mammalian cell lines transducible by the SeF-pseudotyped gp64-null AcMNPV at an m.o.i. of 500 was no longer detectable. An amplifiable SeF-pseudotyped gp64-null AcMNPV vector with greatly reduced tropism for vertebrate cells may have applications in engineering AcMNPV for targeted transduction.
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- Plant
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Effects of dicer-like endoribonucleases 2 and 4 on infection of Arabidopsis thaliana by cucumber mosaic virus and a mutant virus lacking the 2b counter-defence protein gene
More LessIn tobacco and Nicotiana benthamiana, limited cross-protection against cucumber mosaic virus strain Fny (Fny-CMV) was provided by prior inoculation with a deletion mutant lacking the 2b silencing-suppressor protein gene (Fny-CMVΔ2b). Cross-protection by Fny-CMVΔ2b did not result from induction of systemic RNA silencing. We investigated whether protection occurs through induction of localized RNA silencing by using Arabidopsis thaliana plants harbouring mutations in genes encoding the dicer-like (DCL) endoribonucleases 2, 3 and 4 involved in antiviral silencing. In wild-type A. thaliana (Col-0) plants, Fny-CMVΔ2b was symptomless and cross-protected against Fny-CMV infection. Cross-protection by Fny-CMVΔ2b against Fny-CMV infection was not abolished in dcl2, dcl3 or dcl4 mutant plants and was strongest in dcl2/4 double mutants, although in these plants and in dcl4 mutants, Fny-CMVΔ2b replicated to high levels and induced strong symptoms. The results suggest that Fny-CMVΔ2b/Fny-CMV cross-protection is not completely dependent on RNA silencing and also involves competition between these viruses.
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The 3′ untranslated region of cucumber mosaic virus (CMV) subgroup II RNA3 arose by interspecific recombination between CMV and tomato aspermy virus
More LessRecombination in single-stranded RNA viruses is one of the principal mechanisms responsible for their evolution. Here we show, using a variety of different methods, that the 3′ untranslated region (3′UTR) of subgroup II strains of cucumber mosaic virus [CMV(II)] is related more closely to that of tomato aspermy virus (TAV) than to those of CMV(I) strains. These results suggest that the CMV(II) 3′UTR arose by interspecific CMV/TAV recombination. The putative crossover is close to the 5′ end of the 3′UTR, at a recombination hot spot previously observed in short time-frame experiments. The CMV(II) strains show divergence from TAV at specific points along the 3′UTR that most probably indicate adaptive changes due to natural selection. Thus, for the large majority of CMV(II) strains examined, the 3′UTR has two discrete regions, W (nt 1902–1971) and Y (nt 2126–2184), that are more similar to the corresponding regions of TAV than to those of CMV(I) strains.
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- Fungal
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A novel putative virus of Gremmeniella abietina type B (Ascomycota: Helotiaceae) has a composite genome with endornavirus affinities
More LessAscospore and mycelial isolates of Gremmeniella abietina type B were found to contain three different dsRNA molecules with approximate lengths of 11, 5 and 3 kb. The 11 kb dsRNA encoded the genome of a putative virus and is named Gremmeniella abietina type B RNA virus XL (GaBRV-XL). GaBRV-XL probably exists in an unencapsulated state. We identified two distinct dsRNAs (10 374 and 10 375 bp) of GaBRV-XL, both of which coded for the same putative polyprotein (3249 amino acids) and contained four regions similar to putative viral methyltransferases, DExH box helicases, viral RNA helicase 1 and RNA-dependent RNA polymerases. While a cysteine-rich region with several CxCC motifs in GaBRV-XL was similar to that of putative endornaviruses, cluster analyses of conserved regions revealed GaBRV-XL to be distinct from a broad range of viral taxa but most closely related to Discula destructiva virus 3. Collectively, these findings suggest that GaBRV-XL represents a novel virus group related to endornaviruses.
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- Other Agents
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A unicellular algal virus, Emiliania huxleyi virus 86, exploits an animal-like infection strategy
Emiliania huxleyi virus 86 (EhV-86) belongs to the family Phycodnaviridae, a group of viruses that infect a wide range of freshwater and marine eukaryotic algae. Phycodnaviridae is one of the five families that belong to a large and phylogenetically diverse group of viruses known as nucleocytoplasmic large dsDNA viruses (NCLDVs). To date, our understanding of algal NCLDV entry is based on the entry mechanisms of members of the genera Chlorovirus and Phaeovirus, both of which consist of non-enveloped viruses that ‘inject’ their genome into their host via a viral inner-membrane host plasma membrane fusion mechanism, leaving an extracellular viral capsid. Using a combination of confocal and electron microscopy, this study demonstrated for the first time that EhV-86 differs from its algal virus counterparts in two fundamental areas. Firstly, its capsid is enveloped by a lipid membrane, and secondly, EhV-86 enters its host via either an endocytotic or an envelope fusion mechanism in which an intact nucleoprotein core still encapsulated by its capsid is seen in the host cytoplasm. Real-time fluorescence microscopy showed that viral internalization and virion breakdown took place within the host on a timescale of seconds. At around 4.5 h post-infection, virus progeny were released via a budding mechanism during which EhV-86 virions became enveloped with host plasma membrane. EhV-86 therefore appears to have an infection mechanism different from that employed by other algal NCLDVs, with entry and exit strategies showing a greater analogy to animal-like NCLDVs.
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Volumes and issues
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Volume 105 (2024)
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Volume 104 (2023)
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Volume 103 (2022)
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Volume 102 (2021)
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Volume 101 (2020)
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Volume 100 (2019)
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Volume 99 (2018)
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Volume 97 (2016)
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Volume 36 (1977)
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Volume 35 (1977)
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Volume 34 (1977)
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Volume 33 (1976)
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Volume 31 (1976)
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Volume 13 (1971)
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Volume 12 (1971)
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Volume 11 (1971)
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Volume 10 (1971)
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Volume 9 (1970)
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Volume 8 (1970)
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Volume 7 (1970)
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Volume 6 (1970)
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Volume 5 (1969)
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Volume 4 (1969)
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Volume 3 (1968)
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Volume 2 (1968)
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Volume 1 (1967)