13 The Endocytic Pathway and Virus Entry

Abstract

Endocytosis is an essential component of the strategies employed by many animal viruses to enter their host cells. For Semliki forest virus (SFV) or influenza virus, for example, the acidic environment in endocytic organelles triggers conformational changes in the envelope glycoproteins that initiate the membrane fusion events leading to penetration. As fusion is absolutely dependent on exposure to acid pH, and can only occur within endocytic organelles, endocytosis is a prerequisite for the productive entry of these viruses (Marsh and Helenius 1989).

Weak bases, carboxylic ionophores, or specific inhibitors of vacuolar proton ATPases, which neutralize acidic endocytic organelles, inhibit the entry of pH-dependent viruses and can distinguish enveloped and non-enveloped viruses that require exposure to acid pH from those that do not (see, e.g., McClure et al. 1988see, e.g., McClure et al. 1990). As the entry of this latter group is pH-independent, it is frequently assumed that their entry is also independent of endocytosis and occurs by penetration of the plasma membrane (see, e.g., Stein et al. 1987). However, the evidence that penetration at the cell surface can lead to productive infection is scant and often equivocal. In this chapter, we discuss the notion that endocytosis may facilitate the productive entry of both pH-dependent and pH-independent viruses. Furthermore, we discuss the evidence that endocytosis may play additional roles in viral infection and pathology.

ENDOCYTOSIS AND ENDOCYTIC PATHWAYS
Phagocytic and Constitutive Endocytosis
Endocytosis describes the uptake of solutes, small particles, and fluid into membrane-bound intracellular vesicles. Different forms of endocytosis, mediated by distinct biochemical mechanisms...