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Several structures of viral proteins in complex with cellular receptors are now available. However, in very few cases has it been possible to compare structures of different strains of the same virus in complex with the same receptor. The structure-function analysis by Cupelli et al. (p. 3189-3200) shows that the conformation of a protruding adenovirus surface loop differs in two CD46-binding strains, modulating the affinity of receptor binding. This work advances an understanding of how subtle differences at the receptor interface can lead to altered receptor-binding properties, which may lead to changes in viral pathogenicity and tropism.
Borna disease virus (BDV) is an important experimental model for studies of viral neuropathogenesis. The mechanisms governing cell tropism of BDV are unknown. Clemente et al. (p. 3562-3575) developed a small interfering RNA-based high-throughput screen to identify host factors required for BDV cell entry mediated by the viral surface glycoprotein. The screen yielded 24 cellular genes that participate in a broad range of distinct cellular functions, suggesting a complex process associated with BDV cell entry. Screens of this type should be applicable to identification of cellular genes involved in the cell entry of other viruses.
The cytosolic viral RNA receptor, RIG-I, is crucial for the detection of various RNA viruses and activates signaling cascades leading to type I interferon production. Ubiquitination of RIG-I by TRIM25 is essential for its signal-transducing capacity. Gack et al. (p. 3220-3229) show that phosphorylation of the RIG-I caspase recruitment domains inhibits the TRIM25-mediated ubiquitination of RIG-I and thus dampens induction of an antiviral interferon response. This work suggests that RIG-I ubiquitination and phosphorylation antagonize each other, thereby unveiling another level of complexity of the regulation of RIG-I activity.
Expression of PrP glycoprotein is essential for prion neuroinvasion. However, mechanisms that govern spread of the infectious agent from the periphery are not clear. Cancellotti et al. (p. 3464-3475) found that the glycosylation status of host PrP dramatically regulates both incubation time and final targeting of disease in the brain. Intraperitoneal inoculation of transgenic mice expressing different types of glycosylated PrP with two prion strains reveals that diglycosylated PrP facilitates neuroinvasion, whereas mono- and unglycosylated PrP delays or prevents this process. Inoculated mice also display dramatically different pathologies in the central nervous system, suggesting that glycosylation determines routes of transmission.
The genomes of all animals are colonized by endogenous retroviruses (ERVs). Most ERVs are defective and incapable of replication. However, fully infectious ERVs have been identified in several mammalian species. Miyazawa et al. (p. 3690-3694) isolated RD-114, an ERV of cats, in some commercially available vaccines for pets. This study shows that the methods currently employed to screen veterinary vaccines for retroviruses should be reevaluated.