We also observed that expression of HLA-DM was sufficient to induce Gag retention and impede virus release from cells. However, Finzi et al.(2006) did not observe retention in the presence of HLA-DM or HLA-DO [8] . This difference may be explained by their use of a bicistronic construct for expression of the HLA-DM heterodimer; however, this strategy was also used to express HLA-DR, which still induced retention [8] . Irrespective of these differences, Gag retention and loss of virus release correlates with increasing HLA-DR expression. These results do not exclude the possibility that HLA-DR and Gag trafficking may be linked. Indeed, we have demonstrated that Gag co-immunoprecipitates with HLA-DR from CIITA expressing cells and this interaction is independent of the cytoplasmic tails of HLA-DR (data not shown). Further, other HIV proteins may be linked to class II trafficking. Stumptner-Cuvelette et al. (2003) and Chaudhry et al.(2009) , have independently demonstrated that HIV Nef induces internalization of surface class II in epithelial and monocytic cell lines, respectively [37, 64] . However, we did not observe downregulation of HLA-DR from the cell surface, following transfection of the HIV genome into CIITA-expressing epithelial cells (data not shown) or HIV infection of CIITA-expressing CD4+ T cells (unpublished data). Further, Gluschankof and Suzan demonstrated that expression of Gag-Pol restored HLA-DR presence at the cell surface in the H78-C10.0 line, a T cell clone deficient for surface HLA-DR expression [40] . Collectively, our work and that of others suggests a link between HLA-DR and Gag trafficking, where localization may be cell-type dependent.