Читать книгу Principles of Virology - Jane Flint, S. Jane Flint - Страница 220

In animals, viral infections usually begin at the body surfaces that are exposed to the environment (Fig. 5.1; see also Volume II, Chapter 2). Epithelial cells cover these surfaces, and the region of these cells exposed to the environment is called the apical surface. Conversely, the basolateral surfaces of such cells are in contact with adjacent or underlying cells or tissues. These cells exhibit a differential (polar) distribution of proteins and lipids in the plasma membrane that creates the two distinct surface domains. Movement of macromolecules between the cells is prevented by tight junctions (Fig. 5.1).

The first steps in virus attachment are governed largely by the probability of a random collision between a virus particle and a cell, and therefore by the concentrations of free particles and host cells. The rate of attachment can be described by the equation

dA/dt = k[V][H]

where A is attachment, t is time, [V] and [H] are the concentrations of virus particles and host cells, respectively, and k is a constant that defines the rate of the reaction. It can be seen from this equation that if a mixture of viruses and cells is diluted after a period sufficient for adsorption, subsequent binding of particles is reduced greatly. For example, a 100-fold dilution of the virus and cell mixture reduces the attachment rate 10,000-fold (i.e., 1/100 × 1/100).

The initial association of virus particles with cells is probably via electrostatic forces, as it is sensitive to low pH or high concentrations of salt, but higher-affinity binding relies mainly on hydrophobic and other short-range forces. These interactions are usually aided by the extracellular matrix. Extracellular matrices hold the cells and tissues of the body together and are made up of two main classes of macromolecules: glycosaminoglycans (such as heparan sulfate and chondroitin sulfate), which are unbranched polysaccharides made of repeating disaccharides; and fibrous proteins with structural (collagen and elastin) or adhesive (fibronectin and laminin) functions (Fig. 5.1).