Principles of Virus Uncoating: Cues and the Snooker Ball

Abstract

Viruses are spherical or complex shaped carriers of proteins, nucleic acids and sometimes lipids and sugars. They are metastable and poised for structural changes. These features allow viruses to communicate with host cells during entry, and to release the viral genome, a process known as uncoating. Studies have shown that hundreds of host factors directly or indirectly support this process. The cell provides molecules that promote stepwise virus uncoating, and direct the virus to the site of replication. It acts akin to a snooker player who delivers accurate and timely shots (cues) to the ball (virus) to score. The viruses, on the other hand, trick (snooker) the host, hijack its homeostasis systems, and dampen innate immune responses directed against danger signals. In this review, we discuss how cellular cues, facilitators, and built-in viral mechanisms promote uncoating. Cues come from receptors, enzymes and chemicals that act directly on the virus particle to alter its structure, trafficking and infectivity. Facilitators are defined as host factors that are involved in processes which indirectly enhance entry or uncoating. Unraveling the mechanisms of virus uncoating will continue to enhance understanding of cell functions, and help counteracting infections with chemicals and vaccines.

Endosomophagy clears disrupted early endosomes but not virus particles during virus entry into cells     

“…Non-enveloped viruses are membrane-free, except for certain picornaviruses which occur in both enveloped and non-enveloped forms [42]. They all encode membrane-interacting proteins, which are typically encased in a capsid, and can be activated or exposed by cues from the host cell during entry [35] [43]. Activation of membrane-active proteins leads to pore formation, piercing or rupture of the host membrane [44] [45] [46].…”

“…Virus penetration into the cytosol occurs from early endosomes in a pHindependent manner [29] [30]. It requires the membrane-lytic viral protein VI [31] [32] [33], lysosomal secretion, the sphingolipid ceramide [34] [35], and gates the pathway for viral DNA genome separation from the capsid and nuclear delivery of the viral genome [36] [37]. Here, we describe a novel observation, the recruitment of Gal3, ubiquitin and the poly-ubiquitin binding protein p62/SQSTM1 to ruptured early endosomes, followed by clearance of disrupted membranes without clearance of virus particles from the in-fected cell.…”

Suppression of Adenovirus Replication by Cardiotonic Steroids

“…The mechanism by which digoxin and digitoxin inhibit adenovirus replication has yet to be fully characterized. If the drugs are modulating signal transduction, it might be expected that virus replication would be compromised, given the importance of signal transduction for virus entry and trafficking as well as subsequent events in the virus replication cycle (45)(46)(47)(48)(49). In the current study, digoxin and digitoxin usually were added at the end of a 60-min adsorption period, by which time HAdV-C5 genome delivery is complete (50).…”

The nuclear export factor CRM1 controls juxta-nuclear microtubule-dependent virus transport

“…Virus particles (virions) are larger than 20 nm in diameter, and require assistance to undertake the cytoplasmic motility that is necessary to cause infection (Dodding and Way, 2011;Greber and Way, 2006;Radtke et al, 2006). Infection involves motors that directly bind to virions, or move virions in endocytic or secretory vesicles (Greber and Way, 2006;Marsh and Helenius, 2006;Yamauchi and Greber, 2016). While short-range transport of virions often depends on actin and myosin motors (Taylor et al, 2011), long-range cytoplasmic transport requires microtubules, and, in the case of incoming virions, the minus-end-directed motor complex dynein-dynactin (Dodding and Way, 2011;Hsieh et al, 2010).…”