Adenovirus flow in host cell networks

Abstract

Viruses are obligatory parasites that take advantage of intracellular niches to replicate. During infection, their genomes are carried in capsids across the membranes of host cells to sites of virion production by exploiting cellular behaviour and resources to guide and achieve all aspects of delivery and the downstream virus manufacturing process. Successful entry hinges on execution of a precisely tuned viral uncoating program where incoming capsids disassemble in consecutive steps to ensure that genomes are released at the right time, and in the right place for replication to occur. Each step of disassembly is cell-assisted, involving individual pathways that transmit signals to regulate discrete functions, but at the same time, these signalling pathways are organized into larger networks, which communicate back and forth in complex ways in response to the presence of virus. In this review, we consider the elegant strategy by which adenoviruses (AdVs) target and navigate cellular networks to initiate the production of progeny virions. There are many remarkable aspects about the AdV entry program; for example, the virus gains targeted control of a large well-defined local network neighbourhood by coupling several interacting processes (including endocytosis, autophagy and microtubule trafficking) around a collective reference state centred on the interactional topology and multifunctional nature of protein VI. Understanding the network targeting activity of protein VI, as well as other built-in mechanisms that allow AdV particles to be efficient at navigating the subsystems of the cell, can be used to improve viral vectors, but also has potential to be incorporated for use in entirely novel delivery systems.

Recent Advances in Novel Antiviral Therapies against Human Adenovirus

“…These vesicles eventually form endosomes, from which the virus escapes by lysing the early endosomal membrane [ 91 ]. The virions then migrate to the cell nucleus using the cellular microtubule network [ 94 , 95 ]. The capsid proteins are removed during transport, such that only the pVII-wrapped and TP-bound viral DNA enter through the nuclear pore complex [ 96 , 97 , 98 ].…”

Orchestrated efforts on host network hijacking: Processes governing virus replication

“…Viruses can target and navigate multiple cell networks during and after cell infection. For instance, adenovirus particles exert targeted control of a well-defined neighborhood of networks including endocytosis, autophagy, and microtubule trafficking by coupling several processes to a single protein, protein VI [136]. The five processes we reviewed here do not work alone but orchestrate synergistically to rewire cells fate toward a state favorable for virus replication ( Figure 6).…”

“…The clinical and industrial values of these processes are double-sided. On one hand, developing drugs targeting one or several pivotal genes/proteins that foster the five overlapping cellular processes after viral infection (such as protein VI of adenovirus [136]) may enhance and/or create synergistic effect with the current treatment modalities of virus-related diseases. On the other hand, endogenously or exogenously modulating one or multiple processes may increase the yield of viral particles that become vaccines once inactivated.…”

Disparate Entry of Adenoviruses Dictates Differential Innate Immune Responses on the Ocular Surface

“…The hexon protein is the most abundant adenovirus protein, with 240 hexon trimers (720 individual hexon proteins) forming the bulk of the capsid structure. Each of the 12 capsid vertices is formed by a ring of five penton base proteins, from which a trimeric fiber protein protrudes, ending in its distal fiber knob (reviewed in [48]). The infection cycle begins with the binding of the fiber knob to a cell surface receptor.…”