Importance of Viral Late Domains in Budding and Release of Enveloped RNA Viruses

Abstract

Late assembly (L) domains are conserved sequences that are necessary for the late steps of viral replication, acting like cellular adaptors to engage the ESCRT membrane fission machinery that promote virion release. These short sequences, whose mutation or deletion produce the accumulation of immature virions at the plasma membrane, were firstly identified within retroviral Gag precursors, and in a further step, also in structural proteins of many other enveloped RNA viruses including arenaviruses, filoviruses, rhabdoviruses, reoviruses, and paramyxoviruses. Three classes of L domains have been identified thus far (PT/SAP, YPXnL/LXXLF, and PPxY), even if it has recently been suggested that other motifs could act as L domains. Here, we summarize the current state of knowledge of the different types of L domains and their cellular partners in the budding events of RNA viruses, with a particular focus on retroviruses.

The Virus–Host Interplay in Junín Mammarenavirus Infection

“…Tsg101 participation in JUNV release is likely to be mediated through its interaction with Z protein PTAP (Pro-Thr-Ala-Pro) late motif located at the C-terminal domain. This motif was shown to be crucial for efficient arenavirus budding [93,97] as also similarly reported for other RNA viruses [188]. Evidence demonstrated that Tsg101 protein is present in JUNV virions and that the compound-mediated blockade of JUNV-Tsg101 interaction impairs JUNV VLP egress [17].…”

Dynamic, but Not Necessarily Disordered, Human-Virus Interactions Mediated through SLiMs in Viral Proteins

“…One example is the interaction of the viral proteins with the endosomal sorting complexes required for transport (ESCRT) pathway inside the cell. The importance of viral late domains (L domains) has been widely implicated in the viral budding process, and short sequence motifs, P[TS]AP, PPxY, and LYPxL, have been involved in the interaction with the ESCRT pathway machinery [103][104][105]. Such motifs were found to be highly conserved across diverse types of viruses, including Poxviruses [106], Hepatitis C viruses [107], Rhabdoviruses [108], Retroviruses [109], Arenaviruses [110], and Filoviruses [111,112].…”

“…Interactions with the WW domain of ubiquitin ligase enzymes, recruitment of Tsg101, and the ubiquitination by specific ubiquitin ligase enzymes have been shown to facilitate the ESCRT pathway-mediated viral budding [113,114]. The role of ESCRT pathway and viral late domains in viral exit have been extensively reviewed [103,116], including the importance of the ESCRT pathway in different phases of the viral life cycle [117]. [27].…”

Visualization of Retroviral Gag-Genomic RNA Cellular Interactions Leading to Genome Encapsidation and Viral Assembly: An Overview

“…In addition to those main three domains, other domains located at different positions in retroviral Gag display different functions (Figure 1). The non-canonical p8 domain in Murine Mammalian Tumor Virus (MMTV) Gag (Pr77 Gag ) and the p2 domain in FIV Gag (Pr50 Gag ) play a role in Gag-mediated assembly and particle production [56,57], while the p9 domain in Equine Infectious Anemia Virus (EIAV) Gag (Pr55 Gag ), the p2 domain in RSV Gag (Pr76 Gag ), the p6 domain in HIV-1 Gag (Pr55 Gag ), the pp24/pp18 domain in MPMV Gag (Pr78 Gag ) [58,59], and the pp21 domain in MTMV Gag contain common or alternative conserved motifs termed late domains (or L-domains), that specifically recruit the Endosomal Sorting Complex Required for Transport (ESCRT) machinery at viral budding sites to regulate viral budding of nascent virions at PM (Figure 1, for a review see [60]). Additional retroviral domains exhibit a structural role in viral assembly or in Gag multimerization, as, for instance, the p10 domain in RSV Gag [45], or the segment p2, located between NC and CA in HIV-1 Gag [61,62] as mutations in this domain modulate packaging of spliced viral RNAs [63,64].…”