Journal of Virology, October 2005, p. 12615-12616, Vol. 79, No. 20
0022-538X/05/$08.00+0 doi:10.1128/JVI.79.20.12615-12616.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
| SPOTLIGHT |
Articles of Significant Interest Selected from This Issue by the Editors
Hendra Virus Fusion Protein Activated by Cathepsin LThe fusion protein of the newly emerged Hendra virus is proteolytically processed to a disulfide-linked heterodimer, but the cellular protease responsible for this important cleavage event was previously unknown. Pager and Dutch (p. 12714-12720) show that the endosomal protease cathepsin L is involved in the processing of Hendra virus fusion protein and that cathepsin L processing is essential for membrane fusion activity. This study introduces a novel mechanism for initial proteolytic maturation of viral glycoproteins.
RNA Silencing Suppressor from a Double-Stranded RNA Virus
The RNA silencing-based defense and counter-defense interplay has important ramifications for the replication of double-stranded RNA (dsRNA) viruses, because the dsRNA genome itself could conceivably be the immediate trigger and target of host RNA silencing when it is not encapsidated. How such viruses deal with host RNA silencing is poorly understood. Cao et al. (p. 13018-13027) have discovered the first RNA silencing suppressor from rice dwarf phytoreovirus (RDV), a plant dsRNA virus. Pns10 suppresses virus-induced RNA silencing and local and systemic silencing induced by sense RNA but does not interfere with local and systemic silencing induced by dsRNA. These data provide important insights into the replication of dsRNA viruses.
Vaccinia Virus Recruits Host Nuclear Proteins
Vaccinia virus is a member of the orthopoxvirus family, having a DNA genome but replicating in the cytoplasm of the host cell. Oh and Broyles (p. 12852-12860) show that multiple host nuclear proteins colocalize with viral replication complexes in the cytoplasm of the infected cell. These findings indicate that vaccinia virus has ready access to nuclear proteins, hinting at the origin for some essential functions not identified among viral gene products.
Screening of Human Genes Involved in the HIV-1 Life Cycle for Variants Influencing Disease Progression
Susceptibility to human immunodeficiency virus type 1 (HIV-1) is a complex genetic trait in which many host genes influence disease. Bleiber et al. (p. 12674-12680) investigated whether polymorphisms in genes participating in postentry steps of the HIV-1 life cycle modulate disease. Alleles were assessed for their impact on viral replication in purified CD4 T cells from blood donors and HIV-1-infected individuals. The results suggest that distinct alleles of PML, TSG101, and PPIA are associated with rapid disease progression. This study underscores the importance of considering genetic variants in multigene models of HIV-1 susceptibility.
Human Neurons Can Sense Viral Infection and Mount an Innate Immune Response
The nervous system can mount an innate immune response during a viral attack. Glial cells were thought to be the only gatekeeper for sensing infection. Prehaud et al. (p. 12893-12904) now report that human neurons can express TLR-3 and mount innate immune responses after rabies virus and herpes simplex virus type 1 infections or after treatment with dsRNA, a molecular signature of RNA viruses. This work firmly establishes that human neurons, in the absence of glia, have the intrinsic machinery to sense and defend against viral infections.
Innate Resistance of Astrocytes to HIV-1 Is Linked to dsRNA Response Pathways
Brain astrocytes display a curious innate resistance to acute HIV-1 replication characterized by poor expression of structural proteins and new virus despite relatively efficient expression of viral RNA. Ong et al. (p. 12763-12772) show that astrocytes express relatively little TRBP dsRNA-binding protein that functions in part to antagonize the PKR antiviral response. As a consequence, astrocytes display a highly reactive PKR response to HIV-1 dsRNA elements that restricts the production of new HIV-1 virions. This study highlights TRBP as a novel cellular target for therapeutic intervention that may augment innate resistance pathways capable of blocking HIV-1 production in fully permissive cells.
Outcome of HCV Therapy and T-Cell Responses Are Not Directly Linked
Augmentation of hepatitis C virus (HCV)-specific T cells has been postulated as a major mechanism for the drug-induced control of HCV infection during therapy with alpha interferon and ribavirin. Lauer et al. (p. 12979-12988) used a combination of functional and function-independent assays to determine the relationship between therapy and immune response during acute HCV infection. The results indicate that neither a boost of HCV-specific T-cell frequencies nor an induction of basic T-cell functions, but rather a decline of the T-cell response, coincides with drug-induced control of viremia. In addition, persistence of T-cell responses was not a requirement for sustained control of HCV.
A Novel Orally Bioavailable Antipoxvirus Compound Targets a Virulence Factor
Development of antiviral drugs to prevent and treat smallpox virus infection is a high priority within the federal government's strategic plan for national biodefense preparedness. Yang et al. (p. 13139-13149) describe an orally bioavailable small molecule compound (ST-246) that protects mice from lethal orthopoxvirus disease by inhibiting extracellular virus particle formation. Extracellular virus particles play a critical role in disease progression and are essential for long-range virus spread in the host. Thus, inhibiting virus spread without inhibiting virus replication is a valid antiviral strategy. ST-246 represents a compelling start toward development of an antiviral drug for smallpox.
New Compounds Inhibiting HIV Nuclear Localization
Translocation of the HIV preintegration complex into the nucleus is a necessary step in viral replication and an attractive target for anti-HIV drug design. Haffar et al. (p. 13028-13036) describe a compound designed to bind to a nuclear localization signal in the HIV-1 matrix protein. The compound is shown to inhibit HIV-1 replication by specifically reducing the amount of viral DNA in the nucleus. Drugs targeting HIV-1 nuclear import may be good candidates for further development.
Comparative Sequence Analysis of the Human Adenovirus Hexon Gene: Phylogenetic, Taxonomic, and Clinical Implications
The adenovirus hexon constitutes the major capsid protein, presenting epitopes as important targets of neutralizing antibodies in vivo and for the recognition by cytotoxic T cells. It also serves as a basis for the classification of adenoviruses. Ebner et al. (p. 12635-12642) have sequenced this gene from the majority of serotypes, have completed the sequence data of all 51 human adenovirus hexon genes, and performed a comparative sequence analysis. These data provide the basis for a new adenovirus classification scheme and an improved molecular diagnostic system. Moreover, the findings yield information about putative surface epitopes for virus recognition, which may have important implications for future treatment strategies through efficient targeting of any adenovirus serotype.
Journal of Virology, October 2005, p. 12615-12616, Vol. 79, No. 20
0022-538X/05/$08.00+0 doi:10.1128/JVI.79.20.12615-12616.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
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