On reaching the cytosol, another cohort of cytosolic factors engage and ubiquitinate the substrate, targeting it to the proteasome for degradation. To do so, a network of ER factors recognizes and retro-translocates the misfolded protein to the cytosol. By contrast, should a protein misfold in the ER, an endogenous ER quality control system called ER-associated degradation (ERAD) alleviates the build-up of misfolded ER proteins ( Brodsky and Skach 2011 Smith et al. Once a newly synthesized protein is translated and folded properly in the ER lumen, it exits the ER to reach the Golgi apparatus via membrane budding mediated by the COPII complex. Functionally, the rough ER is responsible for translating secretory and transmembrane proteins, whereas the smooth ER possesses specialized roles including lipid and glycogen metabolism (reviewed in Hopkins 1978). Recent studies suggest the membrane sheets correspond to the rough ER whereas the tubules represent the smooth ER ( Voeltz et al. Structurally, the ER is a continuous membranous system consisting of the nuclear envelope, and peripheral sheets and tubules emanating from it ( Voeltz et al. Together, these insights should unveil clues regarding why many viruses select the ER during infection. We will also draw parallels from the mechanisms by which bacterial toxins use the ER for entry. This review focuses on how viruses co-opt the ER to enter, replicate, and assemble in the target cell. 2009), as the organelle many viruses exploit during infection.
Moreover, as a virus commonly manipulates the host immune system to sustain infection, a membrane’s ability to provide the virus with such an opportunity would offer tremendous advantages during the infection course ( Takeuchi and Akira 2009).Ī wealth of data implicates the endoplasmic reticulum (ER), one of the most elaborate membranous networks in a cell ( Shibata et al. Additionally, because viral replication and assembly often occur in the context of virus-induced membranous structures derived from host membranes, the membranous network of choice should accommodate these remodeling reactions ( Miller and Krijnse-Locker 2008). Examples of cellular triggers include receptors, low pH, proteases, chaperones, and reductases. To support entry, the membranous system must possess triggers capable of inducing the necessary conformational changes that facilitate viral membrane fusion or penetration ( Inoue et al. Selecting the suitable membrane system requires several considerations. Thus, the ability to co-opt a host cell entry pathway leading to efficient replication and assembly ultimately dictates the fate of an incoming virus.įor proper entry, replication, and assembly, viruses often rely on the complex membranous network surrounding and residing within the host cell, such as the plasma, endolysosomal, and endoplasmic reticulum (ER) membranes. Successful infection is usually completed when the newly assembled particle is released into the extracellular milieu, in which it can promote another infection round. In contrast, for productive infection, a viral particle must avoid these nonproductive routes and traffic along a pathway that allows it to reach the appropriate replication and assembly site. Alternatively, the virus could be transported to a degradative intracellular compartment in which it is destroyed. In nonproductive infection, the virus may be targeted to and trapped in organelles unsupportive of viral membrane fusion or penetration, events which normally enable the viral nucleic acid access to the host cytosol or nucleus. This interaction induces virus internalization, and initiates a complex journey of the viral particle into the host’s interior that leads to either nonproductive or productive infection ( Mercer et al. To trigger infection, a virus binds to receptors on a host cell’s plasma membrane.
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