BCA2/Rabring7 Targets HIV-1 Gag for Lysosomal Degradation in a Tetherin-Independent Manner

Bca2 (rabring7,rnf115 or znf364) is a ring-finger e3 ubiquitin ligase that was identified as a co-factor in the restriction imposed by tetherin/bst2 on hiv-1. contrary to the current model,in which bca2 lacks antiviral activity in the absence of tetherin,we found that bca2 possesses tetherin-independent antiviral activity. here we show that the n-terminus of bca2 physically interacts with the matrix region of hiv-1 and other retroviral gag proteins and promotes their ubiquitination,redistribution to endo-lysosomal compartments and,ultimately,lysosomal degradation. the targeted depletion of bca2 in tetherin-expressing and tetherin-deficient cells results in a significant increase in virus release and replication,indicating that endogenous bca2 possesses antiviral activity. therefore,these results indicate that bca2 functions as an antiviral factor that targets hiv-1 gag for degradation,impairing virus assembly and release. © 2014 nityanandam,serra-moreno.