Journal of Virology, January 2006, p. 551-552, Vol. 80, No. 2
0022-538X/06/$08.00+0 doi:10.1128/JVI.80.2.551-552.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.
| SPOTLIGHT |
Articles of Significant Interest Selected from This Issue by the Editors
Identification of a Nodavirus Infection IntermediateFlock house virus (FHV) is an icosahedral insect virus of the family Nodaviridae. Walukiewicz et al. (p. 615-622) report identification of an infection intermediate formed during FHV cell entry. The authors observed that only 70% of particles that bound to susceptible cells proceeded to enter, whereas the remainder eluted from the cell surface. The eluted particles did not rebind cells, displayed an acid-sensitive phenotype, had lost a structural protein, and showed morphological alterations. These properties are reminiscent of infection intermediates previously described for picornaviruses and provide important clues about mechanisms by which nodaviruses enter cells and uncoat their genomes.
Cytomegalovirus Enters Epithelial and Endothelial Cells by Endocytosis and Low pH-Induced Fusion Requiring the UL128-150 Genes
Epithelial and endothelial cells are major cell types infected by human cytomegalovirus (HCMV) within the host. Laboratory strains of HCMV infect these cell types poorly, apparently due to propagation in fibroblasts and loss of the UL128-150 genes. Ryckman et al. (p. 710-722) show that a clinical isolate of HCMV enters epithelial and endothelial cells by endocytosis and low pH-dependent fusion, whereas fibroblasts are infected by fusion at the cell surface. An HCMV mutant lacking UL128-150 genes is defective in the capacity to bind and enter epithelial and endothelial cells. These findings point to a critical role for the UL128-150 genes in HCMV cell entry in infected hosts.
Papillomavirus Egress from Endosomes
Papillomaviruses enter host cells via receptor-mediated endocytosis. Efficient infection, but not virus binding and internalization, requires the minor capsid protein, L2, which accompanies the viral DNA to the nucleus. Using pseudoviruses, Kämper et al. (p. 759-768) show that the L2 protein mediates egress of the viral genome from endosomes and demonstrate that this activity maps to the C-terminal 23 amino acids of L2. This peptide displays strong membrane-disrupting activity. The L2 peptide contains a cluster of basic amino acids adjacent to a cluster of hydrophobic amino acids, which differs from classical virus-encoded membrane-penetrating peptides.
Uracil DNA Glycosylase Is Dispensable for HIV-1 Replication and the Antiviral Effects of the Cytidine Deaminase Apobec3G
Human immunodeficiency virus type 1 (HIV-1) packages the host DNA repair protein uracil DNA glycosylase 2 (UNG2) within viral particles. The normal role of UNG is to remove uracil from nuclear DNA, which is necessary for immunoglobulin class-switch recombination. UNG has been proposed to be important for HIV-1 reverse transcription and mediation of the antiviral response to the cellular cytidine deaminase Apobec3G. However, Kaiser and Emerman (p. 875-882) used a natural human UNG–/– cell line as well as cells that express a potent catalytic active-site inhibitor of UNG2 to conclusively show that this enzyme is dispensable for both HIV-1 replication and the antiviral effects of Apobec3G.
AAV2 Genome Packaging through a Capsid Pore at the Fivefold Symmetry Axes
Genome packaging of adeno-associated virus type 2 (AAV2) is thought to be initiated by the interaction of genome-bound Rep proteins with preformed capsids, thereby targeting the genome to the portal of encapsidation. Studies of AAV2 packaging mutants by Bleker et al. (p. 810-820) support the conclusion that the packaging complex, including Rep proteins, binds to a pore at the fivefold axes of symmetry on AAV2 capsids and uses the pore as a portal for DNA translocation into the capsid. Moreover, this work provides evidence that a defined capsid conformation is necessary for successful DNA encapsidation.
Expanding Retroviral Host Range Increases Cytopathogenicity
Generating high levels of genetic diversity is an important evolutionary strategy employed by retroviruses. Avian retroviruses exhibit remarkable variation within their envelope glycoprotein sequences, allowing them to infect a variety of hosts. Rainey and Coffin (p. 562-570) isolated a viral variant that infects all avian cells tested as well as many mammalian cells. Surprisingly, this single-nucleotide variant has not been found in nature, although it must arise frequently and would be predicted to have a significant selective advantage over its parent. Variants such as this may occur as transient intermediates in host range evolution but must quickly acquire additional mutations to attenuate their pathogenicity.
Healthy Cell Cycle in SIV-Infected Mangabeys
Natural hosts for simian immunodeficiency virus (SIV) infection do not develop AIDS, but mechanisms underlying this lack of disease are unknown. Paiardini et al. (p. 634-642) show that, in striking contrast to HIV infection of humans and pathogenic SIV infection of macaques, natural SIV infection of sooty mangabeys is characterized by the preservation of normal cell cycle control in T lymphocytes. This work identifies a new mechanism of disease resistance in natural hosts for SIV and provides a potential therapeutic target for HIV infection.
Natural History of Human RSV with a Duplicated G Segment
Trento et al. (p. 975-984) report G protein-encoding gene sequences of human respiratory syncytial virus (RSV) present in clinical samples isolated in Buenos Aires between 1999 and 2004. These sequences contain a 60-nucleotide duplication in the G protein-encoding gene, first identified in Argentinean group B viruses from 1999, and share common ancestry with other sequences having the duplicated G segment reported worldwide after 1999. This 60-nucleotide natural tag has allowed examination of the molecular epidemiology of human RSV in an unprecedented setting, providing new information about the dissemination capacity and the evolutionary pattern of this important human pathogen.
Infant HIV-1 Variants Are Largely Resistant to Maternal Antibodies
Most infants born to mothers infected with human immunodeficiency virus type 1 (HIV-1) do not become infected; those that do acquire only a subset of maternal viruses. Wu et al. (p. 835-844) show that viruses transmitted to infants are among those that are more resistant to maternal neutralizing antibody, suggesting a role for antibody in limiting HIV-1 transmission in this setting. The transmitted variants tend to have less heavily glycosylated envelope proteins despite their relative insensitivity to antibody neutralization. The panel of vertically transmitted viruses described in this study may be useful for testing the efficacy of vaccines and passive antibody therapies to prevent mother-to-child HIV-1 transmission.
Live-Cell Imaging and Characterization of RSV
Molecular beacons are double-labeled hairpin oligonucleotide probes designed to fluoresce only upon hybridization. Santangelo et al. (p. 682-688) demonstrate, using molecular beacons targeting the viral genome, that the spread of bovine respiratory syncytial virus (bRSV) in living cells can be monitored with high specificity, sensitivity, and signal-to-noise ratio, and the formation of cytoplasmic inclusion bodies can be visualized with fine details. By imaging active virus in living cells, this method can provide a powerful tool for rapidly detecting viral infection, characterizing viral replication, and designing new antiviral drugs.
Journal of Virology, January 2006, p. 551-552, Vol. 80, No. 2
0022-538X/06/$08.00+0 doi:10.1128/JVI.80.2.551-552.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.
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