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.
Highlights
Viruses are ubiquitous obligate intracellular parasites multiplying only within living cells by usurping the cellular machinery of their host to produce progeny virions
The pandemic caused by influenza A (H1N1) in 1918, which led to more than 50 million deaths worldwide, was followed during this last century by many other epidemics and pandemics caused by RNA viruses, that include human immunodeficiency virus (HIV-1), identified in 1983 as the causative agent of the acquired immunodeficiency syndrome (AIDS), which has caused an estimated 34.7 million deaths according to UNIAIDS [4]; ebolaviruses, causing systemic disease with high lethality rate; and coronaviruses, associated with severe respiratory illness, such as the severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome coronavirus (MERS)
The role of endosomal sorting complexes required for transport (ESCRT)-III-associated ALG-2interacting protein X (ALIX) protein in YPXnL-mediated viral budding was first determined in the equine infectious anemia virus (EIAV) context, where yeast two hybrid and GST pull down assays showed that the p9 domain of EIAV directly interacts with ALIX, and that this interaction would depend on the YPDL sequence, as substitutions in this motif inhibited the interaction between p9 and ALIX [62,143]
Summary
Viruses are ubiquitous obligate intracellular parasites multiplying only within living cells by usurping the cellular machinery of their host to produce progeny virions. There are some exceptions to this rule, and it has been demonstrated that viruses such as hepatitis A virus, poliovirus, rotavirus, and norovirus can exit cells non-lytically within vesicles, enclosing themselves into host-derived membranes [5,6,7] As this feature is usually considered as the major difference between enveloped and non-enveloped viruses, viruses using this strategy for cellular egress are sometimes defined as “quasi-enveloped” (see Section 7). For other enveloped RNA viruses, including coronaviruses, flaviviruses, and bunyaviruses, budding occurs at intracellular membranes into the lumen of organelles such as the endoplasmic reticulum (ER), the Golgi apparatus, the ER–Golgi intermediate compartment (ERGIC), and the endosomes In this case, virus egress relies on the cellular secretory pathway, and the viral budding process is mechanistically equivalent at the PM and at cellular organelles, since in both cases it implies the deformation of the membrane during the viral particle envelopment process. Considering the importance of budding process in the viral life cycle, a better comprehension of molecular mechanisms driving this step would constitute an asset to the development of new antiviral drugs that could be effective against multiple viruses
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
