The role of HIV-1 Vpr in promoting the infection of nondividing cells and in cell cycle arrestSharifi, Hamayun J.; Furuya, Andrea M.; de Noronha, Carlos M.C.Current Opinion in HIV and AIDS: March 2012 - Volume 7 - Issue 2 - p 187–194 doi: 10.1097/COH.0b013e32835049e0 FACTORS MODULATING CD4 T-CELL INFECTION: Edited by James Arthos Abstract Author Information Purpose of review The search for the role(s) that HIV-1 Vpr and its HIV2/SIV paralogs Vpr and Vpx play in viral infection and pathogenesis showed that all three engage CRL4 ubiquitin ligase complexes. This association triggers ubiquitination and degradation of cellular substrates. The identity of the ubiquitin ligase substrates is only now beginning to be revealed. This review focuses on recent work that has identified one such substrate and exposed new cellular restrictions to infection. Recent findings Three groups have now described cellular factors that restrict HIV-1 infection in cells of the myeloid lineage. One of these factors, sterile alpha motif- and metal-dependent phosphohydrolase domain-containing protein 1 (SAMHD1), was shown to be depleted through the CRL4 ubiquitin ligase complex in the presence of HIV-2/SIV Vpx. The other restriction can be defeated by Vpx in the absence of at least one part of the ubiquitin ligase complex that triggers SAMHD1 depletion. Another group has shown that the previously described upregulation of natural killer-cell ligands on the surface of HIV-1-infected cells requires the actions of both the cytidine deaminase APOBEC3G and uracil-N-glycosylase 2 in association with HIV-1 Vpr. Summary As more cellular interaction partners are identified for HIV-1 Vpr and its paralogs from other viruses, details are emerging about Vpr function. The recent findings have highlighted the existence of two new human proteins that can act to combat HIV infection and have revealed how HIV-1 proteins act in concert to modulate the interaction between natural killer cells and HIV-1 infected cells. Center for Immunology and Microbial Disease, Albany Medical College, Albany, New York, USA Correspondence to Carlos M.C. de Noronha, ScD, Medical Sciences Building 216, MC-151, Albany Medical College, Albany, NY 12208, USA. Tel: +1 518 262 1175; fax: +1 518 262 6161; e-mail: deNoroC@mail.AMC.edu © 2012 Lippincott Williams & Wilkins, Inc.