Читать книгу Principles of Virology - Jane Flint, S. Jane Flint - Страница 230

Binding of virus particles to cell receptors not only concentrates the particles on the cell surface, but also activates signaling pathways that facilitate virus entry and movement within the cell or produce cellular responses that enhance virus propagation and/or affect pathogenesis. Binding of virus particles may lead to activation of protein kinases that trigger cascades of responses at the plasma membrane, cytoplasm, and nucleus (Chapter 14). Second messengers that participate in signaling include phosphatidylinositides, diacylglycerides, and calcium. Regulators of membrane trafficking and actin dynamics also contribute to signaling. Additionally, virus-receptor interactions can stimulate antiviral responses, such as synthesis of type I interferons (Volume II, Chapter 3).

Figure 5.10 Mechanisms for the uptake of macromolecules from extracellular fluid. During phagocytosis, large particles such as bacteria or cell fragments that come in contact with the cell surface are engulfed by extensions of the plasma membrane. Phagosomes ultimately fuse with lysosomes, resulting in degradation of the material within the vesicle. Endocytosis comprises the invagination and pinching off of small regions of the plasma membrane either by macropinocytosis or by receptor-mediated endocytosis. Macropinocytosis mediates nonspecific uptake of fluids and small molecules. It is triggered by ligands and dependent on actin and signaling pathways different from those required for phagocytosis. Receptor-mediated endocytosis results in the specific uptake of molecules bound to cell surface receptors. Filopodia are actin-rich protrusions that sample the environment and participate in many cellular processes such as migration. Movement along filopodia occurs by an actin-dependent mechanism.

Signaling is essential for the entry of some viruses, such as simian virus 40, into cells. Binding of this virus particle to its glycolipid cell receptor, GM1 ganglioside, causes activation of tyrosine kinases. The signaling that ensues induces reorganization of actin filaments, internalization of the virus in caveolae, and transport of the caveolar vesicles to the endoplasmic reticulum (Fig. 5.6). The activities of more than 50 cellular protein kinases regulate the entry of this virus into cells.