Uptake Penetration

Following attachment, virions can enter cells by one of two mam mechanisms, endocytosis or fusion.

Endocytosis

The majority of mammalian cells are continuously engaged in receplor-medwted endocytosis for the uptake of macromolecules via specific receptors Many enveloped and nonenveloped viruses use this essential cell function to initiate infection (Fig 3-3). Attachment to receptors, which cluster at clathrnt-conted pits, is followed by endocytosis into clathrin-coated vesicles that enter the cytoplasm and, after removal of theclathrin coat, fuse with endosomes (acidic prelysosomal vacuoles). Acidification within the vesicle triggers changes in the capsid protein VP4 of poliovirus, for example, leading to release of RNA from the virion into the cytosol. Likewise, at the acidic pH of the endosomes, the hemagglutinin molecule of influenza virus undergoes a conformational change, which enables fusion to occur between the viral envelope and the endosomal membrane, leading to release of the viral nucleocapsid into the cytoplasm. Many other nonenveloped and enveloped viruses undergo comparable changes.

Fusion with Plasma Membrane

The F (fusion) glycoprotein o! paramyxoviruses causes the envelope of these viruses to fuse directly wifh the plasma membrane of the cell, even at pH 7.

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