Although variation in the entire HLA protein is involved in the differential response to HIV across HLA allotypes, the major genetic effects are condensed to the positions highlighted in this study, indicating a structural basis for the HLA association with disease progression that is probably mediated by the conformation of the peptide within the class I binding groove.

Moreover, we demonstrate that this binding is sufficient to concentrate a recombinant toxin to selectively kill HIV-1-infected cells. Our results suggest that the gp41 C-peptide region is a viable target for development of antiviral therapeutics, neutralizing antibodies, and cytotoxic agents directed against infected cells.

Such a molecule, administered together with agents that induce the expression of dormant integrated provirus (e.g., cytokines or activators of protein kinase C), might help to reduce or possibly eliminate latent reservoirs of HIV-1

A3G and A3A inhibit retrovirus infection by different means.

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.

R111 recombinant is not reactivation-defective because it is able to reactivate in the presence of inhibitors of protein synthesis in the same manner as the WT parent virus, and (b) because the only significant difference in the WT and R111 viruses is the presence of the REST gene in the latter virus, the data suggest that expression of this gene blocks reactivation and that suppression of protein synthesis, including that of REST, enables reactivation.

with dexamethasone or dexamethasone and cycloheximide

Specifically, a stress response generated by virus entry recruits or activates REST to enable the assembly of the HCLR complex. Stress responses have been postulated to activate REST

using the number of unique peptides identified for each protein (Table 1) as a semiquantitative indirect measure of protein abundance in the purified complex, it was also apparent that eIF4G was enriched in the complex with respect to the other proteins isolated.

Independent observations indicate that eIF4G phosphorylation is stimulated during norovirus replication in cell culture and that this phosphorylated form of eIF4G is associated with MNV VPg in infected cells (29). The impact and functional relevance of initiation factor phosphorylation on the norovirus life cycle is currently under study.