Читать книгу Principles of Virology - Jane Flint, S. Jane Flint - Страница 222

The use of the words “attachment factors,” “receptors,” and “coreceptors” can be confusing, particularly as different terminologies are adopted in different manuscripts. Convention dictates that the first cell surface molecule that is found to be essential for virus binding is called its receptor. However, virus particles may initially bind molecules that aid attachment to the cell surface but are not essential for binding, termed attachment factors. Binding to attachment factors is generally nonspecific, mediated by electrostatic interactions, and does not permit virus entry into the cell.

Following specific binding of the viral proteins to the receptor, binding to additional cell surface molecules, known as coreceptors, may be required for entry to occur. The distinction between receptors and coreceptors usually relies on the order in which they are bound; however, this order might be difficult to determine experimentally and can be influenced by cell type and multiplicity of infection. Additionally, a particular cell surface molecule that serves as an attachment factor for one virus may be a receptor for another. The use of these terms is meant to facilitate our understanding, even though it might not be entirely precise.

Example of virus attachment factors, receptors, and coreceptors. The human immunodeficiency virus type 1 envelope glycoprotein mediates all interactions with target cell surface molecules. Electrostatic interactions with heparan sulfate proteoglycans (HSPGs) can enhance the initial attachment of the virus particle for some strains (but can inhibit others). HSPG binding is not required for entry. The primary receptor for human immunodeficiency virus type 1 is CD4, and the CD4 binding site has been precisely mapped on the viral envelope glycoprotein. Interaction with CD4 induces conformational changes that allow the envelope protein to engage a coreceptor, usually CCR5. Binding to CD4 is required for binding to CCR5; hence CCR5 is a coreceptor. Interaction with CCR5 induces further changes in the envelope glycoprotein that result in fusion of the viral and target cell membranes (see text).