Abstract

An additional limitation of previous studies done on human A3 proteins is the reliance on transfecting constructs expressing A3 proteins, which may not reflect the endogenous levels of a protein expression found in vivo

These studies do not determine whether 5-Helix interacts with the native conformation of Env or, rather, some misfolded conformation of gp41 and gp160 on the cell surface.

Other membrane-associated components have also been implicated in RABV binding [20]. By binding one of its receptors, RABV could enter the cell and activate downstream signaling which would allow it to hijack and manipulate axonal transport machineries. Although p75NTR is known to be involved in the retrograde transport of neurotrophic factors, little is known regarding its direct contribution to viral transport.

Possibly, RABV binding to dynein tethers projecting microtubules (MT) in the cell cortex thereby facilitating its retrograde trafficking from the cell periphery. Following this tethering, RABV particles can merge into the RABV-p75NTR endosomes and travel to the neuron cell body.

It was unclear if this was a result of increased expression levels or as a consequence of redistribution of the proteins to the factories. To address this, we monitored protein expression levels of eIF4E, eIF4A1, and eIF4G over the course of an infection. As others have found (39), we were unable to detect any difference in the levels of total protein in mock versus infected cells from 0 to 20 h p.i. (Fig. 3C and data not shown). Together, these data suggest that cellular translation proteins are redistributed to the VF.

Our finding that σNS interacts with eIF3A and pS6R suggests that translational machinery is recruited to the factory by viral proteins. This is consistent with the finding of others that σNS cosediments with 40S and 60S ribosomes (62) and suggests that σNS is directly involved in viral translation.

Thus, VP16, a virion protein brought into the cells during infection, recruits several cellular proteins, including LSD1, to derepress α gene promoters. One α gene product, infected cell protein 0 (ICP0), derepresses β and γ1 genes. Ultimately, the onset of viral DNA synthesis enables the expression of very late, or γ2, genes (4).

In contrast, simultaneous expression of all viral genes during reactivation from latency is likely to minimize yield, but the mission of the virus is to assemble enough viruses to reach the portal of egress from the body (e.g., mouth, genitals) rather than to overwhelm the host with infectious virus.

As these proteins were not identified in both experimental systems and the focus of this study was to determine the role of canonical initiation factors in VPg-dependent translation, these additional host cell proteins factors were not examined in more detail.

Noroviruses, members of the Caliciviridae family of small positive-strand RNA viruses, are a major cause of acute gastroenteritis in man (8) but have also been identified in a number of other species including dogs (9, 10), cats (11), sheep (12), and cattle (13