Journal of Virology, November 2005, p. 13837-13838, Vol. 79, No. 22
0022-538X/05/$08.00+0 doi:10.1128/JVI.79.22.13837-13838.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
| SPOTLIGHT |
Articles of Significant Interest Selected from This Issue by the Editors
Carbohydrate Modifications of Alpha-Dystroglycan Are Important for Arenavirus Receptor Function
Alpha-dystroglycan (
-DG) was identified as a common receptor for lymphocytic choriomeningitis virus (LCMV) and several other arenaviruses, including Lassa fever virus. Genetic and biochemical data demonstrate that -DG is subject to a remarkably complex and highly specific pattern of posttranslational modifications, which are critical for its function in host cells. Using complementary approaches, Kunz et al. (jvi 14282-14296) and Imperiali et al. (jvi 14297-14308) demonstrate that two of these specific posttranslational modifications of -DG, protein O mannosylation (jvi 14297-14308) and modification by the glycosyltransferase LARGE (jvi 14282-14296), are also crucial for -DG recognition by LCMV and Lassa fever virus and for target cell infection. Considering the crucial role of -DG binding affinity for tissue tropism and disease, posttranslational modification of -DG has important implications for the virus-host interaction in vivo.
Adenovirus Exploits the Aggresome Pathway
Adenovirus must rapidly inactivate the cellular MRN protein complex involved in DNA double-strand break repair or viral genomes become concatenated, interfering with DNA replication and packaging. Liu et al. (jvi 14004-14016) show that the two essential E4 proteins along with E1B-55K associate with MRN in PML nuclear bodies and cause their export to aggresomes, which are juxtanuclear cytoplasmic bodies where cellular proteins involved in the ubiquitin-proteasome system are concentrated. Juxtanuclear cytoplasmic bodies containing E1B-55K and p53 first observed in Ad5-transformed cells more than 20 years ago are also aggresomes that contain MRN complexes, but these cellular proteins are not degraded because of the absence of E4orf6.
Lytic Epstein-Barr Virus Infection Promotes Angiogenesis
Angiogenesis, or the formation of new blood vessels, is a critical event for the efficient growth of both B-cell and epithelial cell malignancies. Hong et al. (jvi 13993-14003) show that supernatants from B cells transformed with a lytic-defective (BZLF1-deleted) form of Epstein-Barr virus are highly impaired in promoting endothelial cell tube formation in vitro and contain less VEGF in comparison to supernatants of B cells transformed with wild-type virus. These results suggest that lytically infected cells contribute to the growth of EBV-associated malignancies by enhancing angiogenesis.
The Retroviral Restriction Factor TRIM5 Is a Trimer
Primate TRIM5 proteins mediate species-specific barriers to retroviral infections by targeting the viral capsid after its entry into the host cell. Mische et al. (jvi 14446-14450) demonstrate that TRIM5 proteins assemble into trimers. A trimeric state should allow TRIM5 oligomers to interact efficiently with threefold pseudosymmetrical structures on the retroviral capsid.
Virus Interactions with the IFN Response; a Delicate Balance
Although the paramyxovirus SV5 blocks interferon (IFN) signaling and limits IFN production, its ability to circumvent the IFN response is not absolute. Carlos et al. (jvi 14112-14121) have examined mechanisms by which IFN inhibits SV5 replication. They show that IFN induces alterations in the relative levels of virus mRNA and protein synthesis and causes a redistribution of virus proteins that leads to the enhanced formation of viral cytoplasmic inclusion bodies. This work suggests that the formation of inclusion bodies is a virus defense mechanism that allows the virus to hide from intracellular antiviral and adaptive immune responses.
Interferon-Stimulated Gene (ISG) 15 Functions as an Antiviral Molecule
Alpha/beta interferons (IFNß) play a critical role in the control of viral infection and induce expression of many cellular genes. However, in most cases, it is not known whether these genes function in antiviral defense. Lenschow et al. (jvi 13974-13983) demonstrate that a chimeric Sindbis virus expressing an interferon-induced ubiquitin homolog, ISG15, protects IFNß receptor-null mice from lethal viral infection. This work provides the first direct evidence that ISG15 serves an antiviral function in vivo. Furthermore, this system provides a method for detecting the antiviral function of novel IFN-induced molecules.
Rabies Viral Evasion of the IFN System: Implication of the Phosphoprotein P
The interferon (IFN) response is the first line of defense against viral infections. Viruses have evolved several mechanisms to counteract IFN action. Rabies virus P protein has recently been shown to inhibit IFN production (K. Brózka, S. Finke, and K.-K. Conzelmann, J. Virol 79:7673-7681, 2005). Vidy et al. (jvi 14411-14420) now provide evidence that P inhibits IFN Jak/Stat signaling by preventing nuclear accumulation of STAT1, indicating that P counteracts different steps of the antiviral IFN defense mechanism. Thus, rabies virus is capable of inhibiting multiple arms of host innate immunity by interfering with the IFN pathway, while its neurotropic localization might protect it from adaptative immune responses.
Mimivirus Gene and Genome Duplications Support Early Evolutionary Origin of Large DNA Viruses
Acanthamoeba polyphaga Mimivirus is by far the largest virus known to date. Its recent discovery raised a number of fundamental questions about the boundaries between viruses and cellular life forms. In this report, Suhre (jvi 14095-14101) shows that a large fraction of the mimivirus genes originates from repeated tandem gene duplications as well as from more ancient segmental genome duplication events. Strikingly, the order of magnitude of the duplications is comparable to that commonly observed in bacteria, archeae, and eukaryotes. These findings are compatible with the view that large DNA viruses establish a deeply rooted branch on the tree of life, rather than representing just collections of genes gathered during their passage in diverse cellular host organisms.
Journal of Virology, November 2005, p. 13837-13838, Vol. 79, No. 22
0022-538X/05/$08.00+0 doi:10.1128/JVI.79.22.13837-13838.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
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