A PHD in T cell evasion

Kaposi's sarcoma-associated herpesvirus (KSHV) has evolved a novel means of evading the human immune system: two KSHV proteins, MIR1 and MIR2, cause immune recognition molecules on the host cell surface to be internalized and degraded in the endosome. But how do MIR1 and MIR2 accomplish this? On page 1265, Coscoy et al. present the surprising finding that the viral proteins ubiquitinate their cellular targets, and that this modification causes the immune recognition molecules MHC-I, B7.2, and ICAM-1 to be endocytosed. In addition to uncovering a new use for ubiquitination, the work identifies the first of a new class of ubiquitin ligases.The authors found that the ubiquitination requires the PHD subfamily zinc finger motifs found in the MIR1 and MIR2 membrane-bound viral proteins. In vitro analysis of MIR2 shows that it is an E3 ubiquitin ligase, making it the...