HIV-1 packs in PACSIN2 for cell-to-cell spread

The assembly and release of retroviral particles is driven primarily by the Gag polyprotein precursor, which contains several functional domains: matrix, capsid, and nucleocapsid. The matrix domain directs Gag to the plasma membrane, capsid plays a key role in Gag multimerization during assembly, and nucleocapsid binds to the viral genomic RNA, recruiting it into the assembling virus particle. In addition to matrix, capsid, and nucleocapsid domains, retroviral Gag precursors contain a variety of smaller peptides, some of which harbor short motifs known as “late” domains that promote virus particle release from the infected cell (1, 2). In PNAS, Popov et al. (3) show that ubiquitin modification of HIV-1 Gag recruits the cellular protein PACSIN2 to sites of assembly to promote virus spread at points of cell-to-cell contact. Cells encode a complex machinery that catalyzes membrane scission events that are oriented away from the cytoplasm; these scission events are essential for a variety of key cellular processes, including the abscission step of cytokinesis, and the generation of intralumenal vesicles that bud into late endosomes to form multivesicular bodies. At the core of this membrane scission machinery are the endosomal sorting complexes required for transport (ESCRTs)—ESCRT-0, -I, -II, and -III—and ESCRT-associated factors, such as ALIX and the AAA ATPase Vps4. Retroviral late domains promote virus particle pinching-off from the plasma membrane by recruiting components of this machinery (2). Retroviruses encode three distinct late-domain sequences: Pro-Thr-Ala-Pro (PTAP), Tyr-Pro-Xn-Leu (YPXnL, where Xn represents 1–4 variable amino acids), and Pro-Pro-X-Tyr (PPXY). These three late domains bind directly to the ESCRT-I component Tsg101, ALIX, and NEDD4-family ubiquitin ligases, respectively. Budding of the paramyxovirus PIV5 was shown to be dependent on the host protein angiomotin-like 1 (AmotL1) (4) and … [↵][1]1To whom correspondence should be addressed. Email: efreed{at}nih.gov. [1]: #xref-corresp-1-1