Journal of Virology, October 2008, p. 9305, Vol. 82, No. 19
0022-538X/08/$08.00+0 doi:10.1128/JVI.01694-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.
| SPOTLIGHT |
Articles of Significant Interest Selected from This Issue by the Editors
Flexible Filamentous Plant Viruses Share a Common Helical Symmetry and Coat Protein StructureAlthough there has been speculation about structural relationships among filamentous plant virus families, there has been no direct evidence for such relationships. Kendall et al. (p. 9546-9554) show that soybean mosaic virus (family Potyviridae) has 8.8 coat protein subunits per turn of the virion helix and confirm that potato virus X (family Flexiviridae) has 8.9 subunits per turn. Low-resolution structures of these viruses determined by a combination of cryoelectron microscopy and X-ray fiber diffraction are very similar, suggesting a common coat protein fold that may be characteristic of most or all flexible filamentous plant viruses.
A Novel Linkage between DNA Damage Sensors and Hepatitis C Virus RNA Replication
Hepatitis C virus (HCV) induces double-stranded DNA breaks, leading to genomic instability. However, the role of the DNA damage response in HCV replication is unknown. Ariumi et al. (p. 9639-9646) demonstrate that ataxia-telangiectasia-mutated kinase and checkpoint kinase 2, which function as DNA-damage sensors, are required for HCV RNA replication, possibly via interactions with HCV NS5B RNA polymerase. This work sheds light on an intriguing relationship between RNA viruses and the genotoxic stress response and provides a novel target for treatment of patients with chronic hepatitis C.
Frequency and Spectrum of Adeno-Associated Virus Serotype 8 Vector Integration in the Livers of Neonatal Mice
Development of adeno-associated virus (AAV) as a gene-delivery vector for clinical use requires an understanding of genomic integration frequency and integration site spectrum. Inagaki et al. (p. 9513-9524) quantified AAV integration frequency and identified AAV integration sites in the livers of mice inoculated with an AAV8 vector at birth. AAV integration was found in every one of approximately 103 cells in neonatal mouse liver, and 68% of the integrations occurred in genes. These results provide new information for establishing the risk of AAV-mediated insertional mutagenesis in neonatal livers, which has been shown to occur in mice.
Human Cytomegalovirus Chromosome Undergoes Dynamic Histone Modifications
Human cytomegalovirus DNA is packaged in virions without histones but associates with histones after reaching the nucleus of an infected cell. Cuevas-Bennett and Shenk (p. 9525-9536) now show that histone H3 acetylation at immediate-early promoters is dynamic. Moreover, the time-dependent modulation of activating markers depends on the binding of the virus-encoded IE2 protein at the major immediate-early promoter. This study suggests that the interplay between IE2 levels and genome copy number control the activation state of the viral chromosome.
Basal Budding of Murine Leukemia Viruses Is Independent of the Cellular Endosomal Sorting Machinery
Retroviruses, including murine leukemia viruses (MLVs), exploit the endosomal sorting complex required for transport (ESCRT) for efficient budding. For many retroviruses, budding is achieved by interactions of specific sequences, termed L-domains, in the structural viral Gag protein with different components of this cellular machinery. Sabo et al. (p. 9770-9775) used MLV L-domain mutants and inhibition of the sorting machinery to show that low basal budding and replication of the virus still occur. These findings suggest that MLVs can use an ESCRT-independent mechanism of budding.
Journal of Virology, October 2008, p. 9305, Vol. 82, No. 19
0022-538X/08/$08.00+0 doi:10.1128/JVI.01694-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.
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