Journal of Virology, November 2005, p. 13197-13198, Vol. 79, No. 21
0022-538X/05/$08.00+0 doi:10.1128/JVI.79.21.13197-13198.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
| SPOTLIGHT |
Articles of Significant Interest Selected from This Issue by the Editors
Positive-Strand RNA Virus NTPase/Helicase Is Required To Recruit RNA Replication TemplatesVirus-encoded NTPase/helicase proteins are essential for RNA replication by many positive-strand RNA viruses. Wang et al. (13747-13758) show that an active brome mosaic virus (BMV) NTPase/helicase is required for a late step in recruiting RNA replication templates into the membrane-associated RNA replication complex. The results suggest that BMV RNA templates may be translocated by the NTPase/helicase into a preformed RNA replication compartment, implying possible parallels between assembly of these intracellular RNA replication complexes and nucleic acid packaging into some virions.
Dissection of Hepatitis C Virus Replication Complexes
Hepatitis C virus (HCV) replication takes place at distinct vesicular membrane structures. However, beyond this, little is known about the architecture of these viral replication complexes. Quinkert et al. (13594-13605) provide a detailed quantitative analysis of viral RNA and proteins involved in HCV replication. Their data suggest that each active complex is composed of only a few viral RNAs but multiple copies of the nonstructural proteins, indicating that one or more of these proteins serve a structural role in replication complex formation. This work has implications for the mechanism of viral RNA replication and points to novel strategies for the identification of the requisite host factors.
A Novel Host Protein Involved in Hepatitis C Virus Replication
Hepatitis C virus (HCV) nonstructural proteins are associated with various host proteins that are involved in HCV replication. Hamamoto et al. (13473-13482) show that human vesicle-associated membrane protein-associated protein subtype B (VAP-B), in addition to VAP-A, plays an important role in the replication of HCV RNA. This work provides clues about the molecular mechanisms of HCV replication.
Insight into mRNA Cap Methylation in Nonsegmented Negative-Strand RNA Viruses
The 250-kDa large (L) polymerase proteins of the nonsegmented negative-strand (nsNS) RNA viruses possess enzymatic activities essential for mRNA cap formation. Working with vesicular stomatitis virus, Li et al. (13373-13384) show that single amino acid substitutions at each of four positions, which are predicted to form the catalytic site of a methyltransferase domain of L protein, disrupt mRNA cap methylation and inhibit viral replication. These findings have implications for the cap methylation reactions of other nsNS RNA viruses, and they identify a region of the polymerase against which pharmacologic inhibitors might be targeted.
The Capsid (CA) Domain of Gag Coordinates Retroviral Assembly
Human immunodeficiency virus type 1 (HIV-1) and Rous sarcoma virus (RSV) particles differ in size and morphology. To assess the role of individual Gag domains in assembly, and to determine the nature of these size and morphology differences, Ako-Adjei et al. (13463-13472) constructed and characterized chimeric HIV-1 and RSV Gag proteins. The CA domain was found to be the major determinant of retroviral size and morphology. CA also was found to be the sole determinant of coassembly, as chimeras containing the same CA domain were capable of forming a single particle. This finding suggests that the CA domain alone controls the specificity of coassembly.
LANA of KSHV Induces a Bend in DNA upon Binding
Kaposi's sarcoma-associated herpesvirus (KSHV) replicates its latent genome by using the host DNA synthesis machinery. This process is initiated by the viral latency-associated nuclear antigen (LANA), which binds to two adjacent sites within the origin sequence found in each terminal repeat. Wong and Wilson (13829-13836) show that binding of two LANA dimers to a single origin bends the DNA toward the major groove by 110°. These findings bring LANA into line with other well-characterized viral origin binding proteins, such as the Epstein-Barr virus EBNA1 protein, and suggest that viral replication initiator proteins function in part by establishing a specific architecture at the origin.
Evolution of Hepatitis Delta Virus Genome Sequence during Long-Term Replication in Culture
Hepatitis delta virus (HDV) is capable of establishing prolonged infections in vivo. Using cultured cells that provide the essential small delta protein, Chang et al. (13310-13316) observed that the replication of the HDV RNA genome continued for at least 1 year. Such persistence is similar to the chronic replication observed for viroid RNAs in plants. During the 1 year of replication, the HDV genomes underwent many nucleotide sequence changes. These were predominantly single nucleotide changes, most of which could be explained as a consequence of ADAR editing. Overall, there were 2.1% changes/nucleotide/year. Remarkably, the replication competence of the surviving genomes was unchanged relative to the original HDV.
A Mouse Model of Dengue Fever
The lack of animal models for dengue fever and dengue hemorrhagic fever has hampered efforts to develop vaccines and antiviral agents against this mosquito-borne virus. Bente et al (13797-13799) have reconstituted immunosuppressed mice with human cord blood CD34+ cells and infected these mice with dengue virus in a manner mimicking mosquito transmission. These animals develop clinical signs of dengue fever similar to those observed in humans. This model will be useful in studies of dengue pathogenesis.
Alpha/Beta Interferon Restricts Tropism and Prolongs Neuron Survival after West Nile Virus Infection
West Nile virus is an important cause of arthropod-borne encephalitis in the U.S. There are currently no proven therapies for this disease. Samuel and Diamond (13350-13361) demonstrate that alpha/beta interferon is crucial for survival of mice following West Nile virus infection. Their studies show that interferon restricts viral replication and tropism in peripheral tissues and independently increases survival of infected neurons. This work has implications for the treatment of West Nile virus infection, as interferon therapy late in the course of infection could have beneficial effects in mitigating neuronal injury.
HIV Sequence Diversity Is Substantially Driven by Host CD8+ T-Cell Responses
Sequence diversity of HIV represents a major obstacle to the development of effective vaccines, yet forces influencing the evolution of HIV remain unclear. Allen et al. (13239-13249) demonstrate that the majority of amino acid substitutions arising in HIV following acute infection are associated with immune pressures exerted by host CD8+ T-cell responses. Notably, a stereotypic pattern of acquired mutations was observed, suggestive of biochemical constraints limiting this sequence diversity. Thus, viral evolution following acute HIV infection is not a random process but rather is substantially influenced by adaptive host immune pressures.
Use of Rodent Hepatitis Virus-Like Particles for Vaccine Design
Because the hepatitis B virus core protein self-assembles into virus-like particles (VLPs) that are highly immunogenic, this protein has been proposed as a vaccine carrier platform for the delivery of weak immunogens. However, "pre-existing immunity" and "hybrid-core assembly" problems have limited the application of this technology. Billaud et al. (13656-13666) developed a combinatorial process that used core proteins from rodent hepatitis viruses to circumvent these problems. This work demonstrates that optimal combinations of insert position, C-terminal modification, and insert sequence yield hybrid VLPs useful for vaccine design.
Single Mutations in a Plant Virus Genome Change the Transmitting Vector Species
The most frequent noncirculative transmission of plant viruses involves very specific recognition between the virus and its vector. Moreno et al. (13587-13593) have identified a single residue in the P2 protein of Cauliflower mosaic virus that controls the specific recognition of the aphid vector. Using site-directed mutagenesis, the authors show that alteration of this residue modifies the spectrum of the transmitting aphid species. The fact that one such virus mutant spontaneously appeared, when using solely one aphid species as a vector, indicates that adaptation to new vector species can be extremely rapid.
Journal of Virology, November 2005, p. 13197-13198, Vol. 79, No. 21
0022-538X/05/$08.00+0 doi:10.1128/JVI.79.21.13197-13198.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
| ||||||||||||||||||||||||||||||||||||||||||||||
Copyright © 2009 by the American Society for Microbiology. For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»