Journal of Virology, October 2007, p. 10837, Vol. 81, No. 20
0022-538X/07/$08.00+0 doi:10.1128/JVI.01850-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.
| SPOTLIGHT |
During messenger RNA synthesis, polymerases of viruses in the order Mononegavirales are governed by highly conserved gene-start and gene-end sequences that signal initiation and termination of mRNA. Wang et al. (p. 11499-11506) now show that the mRNA capping machinery of a prototype virus, vesicular stomatitis virus, requires a specific cis-acting element that is also provided by the gene-start sequence. By altering the gene start of a nonessential gene introduced into the viral genome, a panel of viable recombinant viruses that produced uncapped mRNA was generated. This study underscores the unique nature of the capping machinery of the Mononegavirales by demonstrating that the capping enzyme requires specific signals in the RNA.
A Gene Therapy Viral Vector Provides Insight into Ongoing Genomic Instability in Living Animals
Recombinant adeno-associated virus (rAAV), a widely used viral vector for research, is devoid of the integration machinery of wild-type AAV but fortuitously inserts its genetic material into host chromosomal DNA by undefined mechanisms. Inagaki et al. (p. 11290-11303) have developed a novel high-throughput method for identifying rAAV integration sites in nondividing cells. Using this technique, the authors show that DNA palindromes, which potentially form unstable secondary structures susceptible to breakage, are a significant target for rAAV integration in mice. This work provides new insights into the mechanisms of rAAV integration and ongoing genomic instability in various organs in living animals.
Paramyxovirus Polymerase Activity Influences Host Antiviral Responses
The noncytopathic paramyxovirus simian virus 5 (SV5) is a poor inducer of innate antiviral immune responses. Dillon and Parks (p. 11116-11127) show that an SV5 mutant with substitutions in the P polymerase subunit and V accessory protein overproduces RNA and induces beta interferon and apoptosis. Expression of wild-type P protein from the P/V mutant genome decreased viral mRNA levels but also reduced these cellular effects. This work identifies the paramyxovirus polymerase as a key factor in limiting antiviral responses, possibly by controlling aberrant mRNA synthesis.
Natural Aerosol Transmission in a Small Animal Model for Smallpox Infection
There has been renewed interest in animal models for orthopoxvirus infections that mimic human smallpox for evaluation of both vaccines and antiviral drugs. Adams et al. (p. 11084-11095) describe a rabbit model of vaccinia or rabbitpox virus infection that requires a low virus inoculum, exhibits high mortality, and is characterized by natural aerosol-mediated animal-to-animal transmission. The use of this model in the evaluation of an antiviral compound is also described. The model can be used to evaluate aspects of poxvirus pathogenesis and the capacity of vaccines and antiviral drugs to prevent aerosol poxvirus transmission and disease.
A Human Immunodeficiency Virus Type 1 Derivative with 7% Simian Immunodeficiency Virus Genetic Content Is Able To Establish Infections in Pig-Tailed Macaques
Innate restriction factors such as APOBEC3 and TRIM5
family members block infection of human immunodeficiency virus type 1 (HIV-1) in simian cells. Igarashi et al. (p. 11549-11552) describe an HIV-1 derivative (HIVNL-DT5R) containing a 7-amino-acid segment from simian immunodeficiency virus (SIV) CA and the entire SIV vif gene that generates plasma viremia in monkeys and elicits humoral responses against all of the HIV-1 structural proteins but does not cause CD4+ T-lymphocyte depletion or clinical disease. These results extend earlier findings obtained using tissue culture systems at the organismal level.
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