Viral Entry and Receptors

The process of retroviral entry into a target cell represents the first step in the viral infection cycle. It is characterized by a complex series of events that are initiated through the binding of the viral surface glycoproteins to specific receptor molecules on the cell's outer membrane. This interaction is thought to trigger a conformational change in the viral glycoprotein, which then mediates fusion of the lipid bilayers of the cell and viral membranes and allows the genetic material of the virus to be introduced into the host-cell cytoplasm.

The envelope glycoprotein complex of retroviruses includes two polypeptides, an external, glycosylated hydrophilic polypeptide (SU) and a membrane-spanning protein (TM), that together form an oligomeric knob or knobbed spike on the surface of the virion. Both polypeptides are encoded by the env gene and are synthesized in the form of a polyprotein precursor that is proteolytically cleaved during its transport to the surface of the cell (see Chapter 7). These proteins are not required for the assembly of enveloped viral particles, but they do have an essential role in the entry process. The SU domain binds to a specific receptor molecule on the target cell. This binding event appears to activate the membrane fusion-inducing potential of the TM protein and, by a process that remains largely undefined, the viral and cell membranes then fuse. The specificity of the SU/receptor interaction defines the host range and tissue tropism of a retrovirus; viral particles lacking envelope glycoproteins are noninfectious, and cells lacking a receptor are nonpermissive for viral entry. Viruses may bind weakly to resistant cells through relatively nonspecific interactions, but, in the absence of a specific receptor molecule, they are unable to initiate the infection process.