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Alterations to RNA secondary structures in the untranslated regions of positive-strand RNA virus genomes can result in attenuation. Bailey et al. (p. 2859-2870) now demonstrate that although a variable polypyrimidine (U/C) tract in the 3′ untranslated region of the murine norovirus genome is dispensable for virus replication in cell culture, its removal affects virulence in the natural host. This is the first report of a role for RNA structures in calicivirus virulence and highlights possible strategies for rational attenuation of noroviruses for the development of vaccines.
Bacterial artificial chromosomes encoding herpesvirus genomes are common tools for engineering mutant viruses. However, the residual vector sequences in the viral genomes often cause undesirable genetic and phenotypic alterations. Zhou et al. (p. 2871-2880) describe a new method for efficient excision of vector sequences by using natural viral terminal repeat sequences. The high excision rate also suggests that this strategy can be used for transient gene expression and studies of homologous recombination of terminal repeats in cells.
The N-terminal region of adenovirus E1A cooperates with the ras oncogene to transform primary epithelial cells, whereas the C-terminal region suppresses oncogenic transformation. The oncogenesis-restraining activity of the E1A C-terminal region was previously attributed to interaction of E1A with the cellular corepressor CtBP. Komorek et al. (p. 2719-2731) now show that the transformation suppression activity of the E1A C-terminal region is also mediated via interactions with FOXK1/K2 transcription factors and dual-specificity protein kinases DYRK1A/1B and HAN11. The E6 proteins of benign cutaneous human papillomavirus types 14 and 21 also interact with FOXK1/K2 through a sequence motif similar to the E1A motif, which restricts cell transformation.
Immunodeficient mice engrafted with human immune cells are tractable models for studies of HIV-1 infection. Ince et al. (p. 2740-2752) describe features of viral envelope glycoprotein (Env) evolution in a humanized mouse model and compare this process to that seen in human infection. Changes in Env associated with replication were observed in the absence of antibody selection, including increased neutralization sensitivity to specific antibodies, suggesting that the observed Env changes function in coreceptor switch. These findings highlight the utility and limitations of this model for analysis of chronic HIV-1 infection.
Elderly subjects display a relatively high level of resistance to disease caused by the current pandemic influenza virus, 2009 A (H1N1). Krause et al. (p. 3127-3130) found that antibodies induced by natural infection of humans with the 1918 influenza virus also neutralize the 2009 virus and can ameliorate disease in mice inoculated with the 1918 virus. The epitope recognized by these unusual antibodies is preserved in circulating porcine influenza viruses throughout the 20th century, which provides a molecular basis for the immunity of the elderly to the current pandemic strain.