Journal of Virology, September 2005, p. 10837-10838, Vol. 79, No. 17
0022-538X/05/$08.00+0 doi:10.1128/JVI.79.17.10837-10838.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
| SPOTLIGHT |
Articles of Significant Interest Selected from This Issue by the Editors
Down-Regulation of p53 by dsRNA and Its Implications for the Use of Oncolytic Viruses and Viral Vectorsp53, a well-known tumor suppressor, has recently been shown to participate in the antiviral response against vesicular stomatitis virus. Marques et al. (p. 11105-11114) observed that some viruses induce down-regulation of p53 through activation of the PKR and RNase L pathways by dsRNA formed during viral replication. Importantly, these results suggest that viral vectors used to deliver suicide genes to tumor cells or oncolytic viruses may also inadvertently cause down-regulation of p53, which would impair subsequent responses to antineoplastic therapy.
HSV-1 DNA Is Transported in Unenveloped Capsids in Axons In Vivo
Studies of herpes simplex virus assembly in neurons in vivo have been limited by the inability to experimentally manipulate neuronal infection in situ. La Vail et al. (p. 11142-11150) approached this problem by infecting retinal ganglion cells in mice with replication-competent and replication-defective mutant viruses. EM immunohistochemistry, PCR, and a novel in situ DNA hybridization procedure were used to track the anterograde axonal transport of viral DNA. This work establishes that viral DNA replication is necessary for axonal targeting of viral genomes and that the viral DNA is conveyed in unenveloped capsids in mature axons.
CD46-Utilizing Adenoviruses Alter C/EBPß-Dependent Cytokine Expression
Certain subgroup B and D adenoviruses (Ads) use CD46 as the primary attachment receptor. Iacobelli-Martinez et al. (p. 11259-11268) demonstrate a profound reduction in proinflammatory cytokine expression by human peripheral blood mononuclear cells exposed to CD46- but not CAR-utilizing Ad serotypes. In addition, the authors identify a specific transcription factor involved in cytokine expression that is preferentially downregulated following CD46 ligation. These studies contribute new knowledge about Ad-specific immune responses that may influence the generation of Ad vectors for use in gene delivery and vaccine development.
Brain-Specific HERV Activity Profiles and Their Potential Impact on Neurological Disorders
The involvement of human endogenous retroviruses (HERVs) in neuropsychiatric diseases such as schizophrenia is controversial. In a microarray-based study, Frank et al. (p. 10890-10901) establish a human brain-specific HERV activity profile. Comparing this signature to HERV activity in brain samples from individuals with schizophrenia or bipolar disorders, no clear-cut disease associations were detected, although some HERV-K elements were found overrepresented in both disease groups. The results of this study serve as a basis for future investigations of the role of retroviral elements in human CNS disorders.
Neurons Infected by West Nile Virus Initiate an Antiviral Immune Response
West Nile virus (WNV) encephalitis is characterized by neuronal infection and lymphocytic inflammatory infiltrates. The molecular cues that direct lymphocyte recruitment into the central nervous system during WNV infection are unknown. Klein et al. (p. 11457-11466) demonstrate that in response to WNV infection, neurons secrete the chemokine CXCL10, which recruits effector CD8+ T cells for the purpose of viral clearance. This work demonstrates that neurons direct the WNV-specific inflammatory response and identifies CXCL10 as a novel neuroprotective agent.
HAV Escapes the Innate Immune Response by Inhibition of RIG-I-Mediated IFN-ß Induction
Hepatitis A virus (HAV) is a noncytopathogenic, interferon (IFN)-sensitive picornavirus. Elimination of HAV in vivo is dependent on cytotoxic T lymphocytes, whereas in cell culture HAV establishes a persistent infection. Fensterl et al. (p. 10968-10977) show that HAV prevents the dsRNA-induced IFN response in cell culture by suppressing RIG-I-mediated IRF-3 activation and subsequent IFN-ß expression. This strategy allows the virus to evade the innate immune response during its remarkably slow infectious cycle.
Hemagglutinin-Specific Antibodies Mediate Measles Virus Neutralization
Measles virus-neutralizing (MVN) antibodies are directed to the hemagglutinin (H) or fusion protein (F). De Swart et al. (p. 11547-11551) depleted specific antibodies from polyclonal sera of vaccinated subjects by cocultivation with either H- or F-transfected cells. Depletion of F-specific antibodies had little effect on MVN titers, whereas depletion of H-specific antibodies resulted in almost complete abrogation of MVN activity. This work demonstrates that measles vaccination-induced MVN antibodies are mainly directed to the H protein. The approach used in this study may be of value in determining the role of protein-specific antibodies in other virus infections.
Long-term Herpes-specific Antibody Production in Neuronal Tissue
Herpes simplex virus type 2 (HSV-2) establishes latent infection of neurons in sensory ganglia. An HSV-specific serum antibody response develops after initial infection and is maintained by long-lived plasma cells located primarily in the bone marrow. Milligan et al. (p.11537-11540) have now detected HSV-specific, IgG-secreting plasma cells in sensory ganglia and spinal cord of animals long after the establishment of latency. The long-term presence of an antibody response in neuronal tissues has implications for current views of HSV-2 latency, protection against HSV-2 re-infection of neuronal tissue, and modulation of reactivation from latency.
Goose Parvovirus Expression Exhibits Features of both the Dependovirus and Parvovirus Genera of the Parvovirinae
Goose parvovirus (GPV) is an autonomously replicating member of the Parvovirinae family that has recently been classified in the helper-dependent Dependovirus genus. Qiu and Pintel (p. 11035-11044) have found that the expression strategy of GPV is a surprising combination of features previously found exclusively in either the Dependovirus genus, which is primarily composed of the human adeno-associated viruses, or the Parvovirus genus, which is primarily composed of autonomously replicating animal viruses. Thus, this avian parvovirus may represent an evolutionary variant, intermediate, or precursor of animal and human parvoviruses, and its study may provide insights into parvovirus evolution.
Divergence of the Proposed Genetic and Phenotypic Markers of Highly Pathogenic Avian Influenza Viruses
The highly pathogenic (HP) form of avian influenza (AI) impacts international trade of poultry and poultry products. Lee et al. (p. 11412-11421) describe the pathogenic potential of the recent H5N2 AI virus that meets the World Organization for Animal Health (WOAH) molecular criterion for classification as HPAI but is not virulent in experimentally inoculated chickens. Remarkably, the BXBR motif at the hemagglutinin cleavage site without a nearby carbohydrate was not the minimal requirement for the virus to be HP. This study necessitates reexamining what should be considered a reportable virus by WOAH standards.
Journal of Virology, September 2005, p. 10837-10838, Vol. 79, No. 17
0022-538X/05/$08.00+0 doi:10.1128/JVI.79.17.10837-10838.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
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