Molecular Signaling and Cellular Pathways for Virus Entry

The cell signaling plays a pivotal role in regulating cellular processes and is often manipulated by viruses as they rely on the functions offered by cells for their propagation. The first stage of their host life is to pass the genetic materials into the cell. Although some viruses can directly penetrate into cytosol, in fact, most virus entry into their host cells is through endocytosis. This machinery initiates with cell type specific cellular signaling pathways, and the signaling compounds can be proteins, lipids, and carbohydrates. The activation can be triggered in a very short time after virus binds on target cells, such as receptors. The signaling pathways involved in regulation of viral entry are wide diversity that often cross-talk between different endocytosis results. Furthermore, some viruses have the ability to use the multiple internalization pathways which leads to the regulation being even more complex. In this paper, we discuss some recent advances in our understanding of cellular pathways for virus entry, molecular signaling during virus entry, formation of endocytic vesicles, and the traffic. 1. Introduction Unlike the other organisms, in order to create its progeny, viruses need the hosts to provide the replicate resources. In order to deliver their genomes into the host cells for their own purposes, viruses have to overcome the barrier of the cell, the plasma membrane. There are several viral entry ways that have been identified, like genetic injection including phages and membrane fusion such as human immunodeficiency virus type 1 (HIV-1) [1]. The cell endocytic mechanism also provides a route for virus internalization. Recent research has discovered that numerous viruses favor the endocytosis as clathrin-mediated endocytosis (CME) [2–7], caveolae/lipid raft-mediated endocytosis [8–10], macropinocytosis [11–13], and several other unusual pathways [14, 15] by eliciting the endocytic signaling pathways. This review focuses on the elements that are involved in regulating the mechanism of virus entry and their traffic systems. 2. Clathrin-Dependent Endocytosis Although many viruses had shown that their internalization relied on the CME [2–7], the signals that are triggered by viruses are more complicated for their own benefits. Many viruses are low-pH-dependent for their conformation change [16, 17] that is required for membrane fusion or viral particle uncoating, and the endosomes provide this acidic compartment. Therefore, the viruses that entry the host cells via clathrin-mediated endocytosis in most cases will form the