|Home | About | Journals | Submit | Contact Us | Français|
Varicella-zoster virus (VZV) does not attach to receptors used by herpes simplex virus. Instead, insulin-degrading enzyme (IDE) has been proposed as a possible VZV receptor. Carpenter et al. (p. 847-855) provide evidence that IDE is not a cell surface receptor for VZV. Cytosolic IDE binds mainly to an unglycosylated VZV gE precursor found in the endoplasmic reticulum (ER). Because this interaction occurs in the ER, it is possible that VZV gE precursor-IDE engagement is a marker for ER stress and the unfolded protein response following VZV infection.
Hepatitis C virus (HCV) infects only humans and chimpanzees, using four essential entry factors (SR-BI, CD81, claudin, and occludin). Among these, CD81 and occludin are employed in a highly species-specific fashion. Haid et al. (p. 964-975) show that, for genotype 2a HCV, mouse claudin-1 is an inefficient entry factor in human HuH6 liver cells but not in human 293T embryonic kidney cells. These results suggest that claudin-1 contributes to the restricted tropism of HCV and that species-specific utilization of this host factor is modulated by cell-type specific cofactors.
Alternative splicing of prototype adeno-associated virus type 2 (AAV2) P19-generated pre-mRNAs generates transcripts encoding the small Rep proteins Rep40 and Rep52. These proteins differ in their carboxyl termini and are required for optimal packaging of AAV2 genomes. In contrast, small Rep-encoding P19-generated transcripts of AAV5 are primarily polyadenylated within the viral central intron and thus not efficiently spliced. Farris and Pintel (p. 1193-1197) demonstrate that, although precluded from using alternative splicing to generate multiple small Rep isoforms, AAV5 ensures production of a Rep40-like protein by efficiently utilizing a novel internal translation initiation event. This work expands an understanding of AAV gene expression.
Similar to other structural class I viral fusion proteins, the paramyxovirus fusion (F) protein has a conserved heptad repeat A region that regulates F protein activation and membrane fusion. The heptad repeat A regions of class I fusion proteins are also attractive targets for antiviral inhibitors. Luque et al. (p. 810-821) show that a mutation in heptad repeat A increases the membrane fusion activity of the Sendai virus F protein and results in delayed virus clearance and more extensive inflammation in the lungs of mice. This work suggests a direct link between F-mediated membrane fusion and in vivo virulence. Thus, fusion inhibitors may provide a therapeutic advantage by decreasing both virus replication and cell-cell fusion.