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In this article we will discuss about the entry of adenovirus in host cell through attachment and endocytosis steps.
The virus enters into the host cell through the steps as given below:
(a) Attachment:
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Attachment to cells is rather slow and takes several hours to reach a maximum. Viral entry occurs into the two stages. An initial interaction of the fibre protein occurs with a range of cellular receptors. Adenovirus enters into the host cell initiating by the knob domain of the fiber protein which binds to the cell receptor.
There are two currently established receptors: ‘CD46 receptor’ (for the group B human adenovirus serotypes) and the ‘coxsackievirus adenovirus receptor’ (CAR) (for all other serotypes).
There are some other receptors also such as MHC I molecules and sialic acid residues. Thereafter, the secondary interaction (or co-receptor interaction) takes place, where a specialized motif in the penton base protein interacts with an integrin molecule of host cell surface (Fig. 17.7).
(b) Endocytosis:
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Wu and Nemerow (2004) have found that the co-receptor interaction, via an arginine-glycine-aspartatee motif in the adenoviral penton capsid protein, stimulates internalization of the adenovirus. The co-receptor molecule is αv integrin.
Binding to αv integrin results in endocytosis of the virus particle via clathrin-coated pits. Attachment to αv integrin stimulates cell signaling resulting in induction of actin polymerization. Finally, virion enters into the host cell within an endosome (Fig. 17.8).
The penton base protein then binds to the integrin family of cell surface heterodimers and allows internalization of particles via receptor-mediated endocytosis. Most cells express primary receptors for the adenovirus fibre coat protein; however, internalisation is more selective.
Now the viral capsid is located inside the endosome. The endosome acidifies the virus resulting in changes in its topology by disassociating the fibres and capsid. The virion is released into the cytoplasm due to changes in capsid and the toxic nature of the pentons. The virion devoid of fibres is transported to the nuclear pore complex with the help of cellular microtubules (Fig. 17.8).
