The cell biology of receptor-mediated virus entry

Grove, Joe; Marsh, Mark

Within an infected cell, viral nucleic acid, be it RNA or DNA, is relatively cosseted by cellular membranes and a protective cytosolic environment, but the cell-free stage that viral genomes must transit to access new host cells is fraught with danger. Viruses mitigate against these risks by packaging their nucleic acid into particles protected by a membrane and/or protein shell. This packaging poses a thermodynamic dilemma for a virus: particles must be resilient enough to protect the genome from environmental and/or immunological insults but also appropriately labile to ensure the contents are released when encountering suitable target cells. Thus, viruses are constructed as metastable molecular assemblages that can be unlocked during entry by specific molecular and/or cellular environmental cues, with minimal energetic input (Marsh and Helenius, 2006) . Receptors are key to the unlocking process, either directly triggering the molecular changes that lead to fusion/penetration or by guiding virions to specific cellular sites where environmental cues trigger fusion/penetration and subsequent infection. Thus, the unlocking process is usually directly coupled to the mechanisms through which viral genomes are transferred across a limiting cellular membrane (usually the plasma membrane or endosome membrane), the principal barrier to infection.