Steps in virus replication

Attachment: viruses have evolved to the point where they can utilize a wide range of

essential host cell surface protein as receptors. They bind with their own receptor-binding

proteins (ligands) to the receptors on the host cell plasma membrane. Virus receptors on

cells could be glycoproteins or glycolipids. The interaction between the virus receptorbinding

proteins and the corresponding receptor on the host cell contributes to host

specificity.

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Entry: following attachment, the virus gains access to the host cell internal environment

where replication takes place. Viruses employ three different mechanisms for this

internalization:

I. Receptor-mediated endocytosis (viropexis): The site of virus attachment to the plasma

membrane is coated internally with the protein clathrin and the virus-receptor complex

is taken into the cell in a manner similar to phagocytosis. A cage-like lattice, in form of

endosome (vesicle) is then formed after internalization. Fusion of the endosome with

lysome degrades the membrane and the nucleocapsid of the virus is released (seen in

rhabdoviruses, orthomyxoviruses and flaviviruses). Acidification of the clathrin coated

cage-like structure within the host cell cytoplasm also leads to breakdown of the viral

structures in certain viruses.

II. Fusion of viral envelope with the plasma membrane of the host cell (seen in

retroviruses, herpesviruses and paramyxoviruses)

III. Direct introduction of viral genome into the cytoplasm (injection) through channels in

the plasma membrane. This is seen in some non-envelope viruses such as

picornaviruses.

Uncoating: this implies the release of viral genome from the nucleocapsid for

transcription to take place. However, in certain viruses, transcription may proceed

without complete release of the viral genome. The genome of reoviruses may be fully

expressed without being fully uncoated. The mechanism involved in the process of

uncoating is not fully understood. Uncoating may occur on the cell membrane,

cytoplasm, or nucleus and is facilitated by celluar enzymes in some viruses. In

poxviruses, uncoating takes place in two stages. The initial stage is facilitated by host cell

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enzymes while the later stage is mediated by virus-specified proteins. In non-envelope

viruses, uncoating may be due to proteolytic activity of lysosomal enzymes. Uncoating

leads to loss of virus infectivity.