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Journal of Virology, January 2006, p. 18-19, Vol. 80, No. 1
0022-538X/06/$08.00+0 doi:10.1128/JVI.80.1.18-19.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.
| SPOTLIGHT |
Articles of Significant Interest Selected from This Issue by the Editors
A Simple Receptor-Decorated Liposome Model for Studying Cell Entry of Nonenveloped VirusesDuring infection, poliovirus binds to its receptor and undergoes conformational changes that ultimately result in release of the genomic RNA into the cell. The details of this process are poorly understood. Tuthill et al. (p. 172-180) report the development of a simple model system in which liposomes containing NTA head groups are used to capture His-tagged ectodomains of the poliovirus receptor. The receptor-decorated liposomes bind virus and initiate conversion to membrane-anchored intermediates that are indistinguishable from those seen during infection. This model provides a powerful tool for biochemical and structural characterization of cell entry mechanisms employed by poliovirus and other nonenveloped viruses.
SUMOylation of Murine Leukemia Virus Capsid Protein Early in Infection
The murine leukemia virus (MuLV) capsid protein (CA) was shown to bind both the E2 and E3 SUMO-conjugating enzymes at distinct sequence motifs. In this study by Yueh et al. (p. 342-352), CA was noted to be modified by SUMO addition in vivo. Nonbinding mutants of CA were generated and found not to be SUMOylated. Replication of the mutant viruses was blocked early in infection, after reverse transcription but before the formation of nuclear viral DNAs. These results suggest that CA SUMOylation is essential for proper trafficking of the MuLV preintegration complex into the nucleus.
Hepatitis C Virus RNA Must Be Unwound For Replication
The hepatitis C virus (HCV) NS3 protein cleaves the viral polyprotein, hydrolyzes ATP, unwinds RNA (and DNA), and displaces nucleic acid-binding proteins. To examine the role of RNA unwinding in replication, transcription, translation, and polyprotein processing, Lam and Frick (p. 404-411) introduced amino acid substitutions into a subgenomic replicon. Replicons expressing NS3 proteins that hydrolyze ATP, bind nucleic acids, and unwind DNA, but not RNA, fail to replicate. Since the mutant replicons express and process an HCV polyprotein, this work demonstrates that NS3-catalyzed viral RNA unwinding is a critical step in HCV replication.
Mechanism of Lamin B Disruption By Herpes Simplex Virus
The nuclear lamina potentially precludes herpesvirus nucleocapsids from budding at the inner nuclear membrane. Park and Baines (p. 494-504) show that lamin B is partially mislocalized from the nuclear lamina in herpes simplex virus (HSV)-infected cells and that this mislocalization correlates with lamin B phosphorylation and recruitment of protein kinase C to the nuclear rim. A viral protein complex at the nuclear membrane essential for nucleocapsid budding is required for these effects. These results suggest that cellular mechanisms for disrupting the nuclear lamina are co-opted by HSV to promote nucleocapsid envelopment.
Bluetongue Virus Exit Exploits Cellular Exocytic Pathway
Retroviruses and other enveloped viruses that bud at plasma or endosomal membranes recruit cellular protein Tsg101, a component of the ESCRT-I complex. In this report, Wirblich et al. (p. 460-473) show that the NS3 and NS3A proteins of the nonenveloped orbivirus bluetongue virus also recruit Tsg101 to facilitate virus release from infected cells. The capacity to usurp a cellular protein export pathway highlights a common route for export of enveloped and nonenveloped viruses through the plasma membrane.
New Poxvirus Virulence Factor Identified
Poxviruses infect humans and a wide range of animals, frequently jumping from one host to another. Roper (p. 306-313) has identified a new poxvirus virulence factor (vaccinia virus A35R) that is conserved in mammalian-tropic poxviruses. Deletion of the gene does not change growth characteristics or morphogenesis of the virus in tissue culture but attenuates virus infection in mice. A35 is a soluble cytoplasmic protein that shares little homology with nonpoxvirus proteins. Therefore, it is likely involved in a novel virulence mechanism acting intracellularly.
Regulation of Herpes Simplex Virus Entry into Latent or Lytic Transcription in Neurons
In the context of trigeminal ganglion sensory neurons in vivo, herpes simplex virus can enter a state of profound transcriptional repression. Factors regulating entry into latent or lytic replication programs are not fully understood. However, replication of the viral genome within the neuron has long been considered a defining regulatory step. Sawtell et al. (p. 38-50) show that viral DNA replication in neurons per se does not regulate entry into the lytic cycle. Significantly, roles of specific viral genes at all points along the reactivation pathway can now be examined by using new strategies to detect and quantify individual neurons exiting the latent transcriptional program. This work may allow a precise dissection of key regulatory checkpoints governing reactivation of lytic infection.
Gamma Interferon Blocks Gammaherpesvirus 68 Reactivation from Latency
Latency establishment and reactivation are critical aspects of gammaherpesvirus pathogenesis. A fundamental question is whether the maintenance of latency is governed by interactions between the virus and the parasitized cell, factors expressed by host immune cells, or both. Steed et al. (p. 192-200) demonstrate that gamma interferon (IFN
) inhibits the reactivation of murine gammaherpesvirus 68 from latency. IFN regulates viral gene expression in vivo during latency, and depletion of IFN after the establishment of latency increases the frequency of viral reactivation. Thus, IFN is required for host immune surveillance against reactivation of a gammaherpesvirus from latency.
Prostate Tumor Cells Are Eliminated by Cytotoxic T Lymphocytes Induced by an Oncolytic Influenza Virus
Oncolytic viruses are promising agents in the treatment of cancer. However, these viruses are unlikely to completely eliminate tumor cells in vivo. Efferson et al. (p. 383-394) used a prostate tumor cell model to show that an attenuated influenza virus with oncolytic properties has only weak oncolytic activity. Nevertheless, tumor cells were efficiently eliminated in vitro by combining virus infection with the addition of peripheral blood mononuclear cells and interleukin-12, resulting in the induction of tumoricidal cytotoxic T lymphocytes (CTL). Integration of viral oncolysis and CTL differentiation represent a promising new approach for the therapy of cancer.
Recombination in Human Enteroviruses: Dynamics and Constraints
Recombination within and between enterovirus serotypes contributes to the genetic diversity of these viruses. Simmonds and Welch (p. 483-493) observed species-associated differences in the dynamics of recombination in a population-based enterovirus survey in Scotland, with species B enteroviruses demonstrating many more frequent, time-correlated recombination events than those found in species A. Using new phylogenetic tools, the authors observed sharply demarcated boundaries between the VP2/VP3/VP1 structural gene block and sequences 5' and 3' to this region where recombination events were detected. These findings provide fresh insights into the dynamics of picornavirus recombination and highlight the value of structured sampling in documenting the emergence of novel recombinant forms in human populations.
Journal of Virology, January 2006, p. 18-19, Vol. 80, No. 1
0022-538X/06/$08.00+0 doi:10.1128/JVI.80.1.18-19.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.
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