The following points highlight the six main stages involved in the replication of animal viruses. The stages are: 1. Adsorption 2. Penetration 3. Un-Coating 4. Replication of Viral Genome 5. Synthesis and Assembly of Virus Capsids 6. Release of New Virus.
Stage # 1. Adsorption:
Adsorption to the host cell surface is the first step in reproduction cycle of animal viruses. Adsorption of virion to the host cell surface takes place through a random collision of virion with a plasma membrane receptor site; the receptor is a protein, and frequently a glycoprotein. Animal viruses, like bacteriophages, possess attachment sides with the help of which it attaches to the receptor site.
Besides of glycoprotein receptors, sometimes, a complex carbohydrate (e.g., heparan sulfate) is the receptor, these receptors vary in their distribution pattern on plasma membrane and this distribution variation plays a key role in tissue and host specificity of animal viruses.
For instance, poliovirus receptors are found only in human nasopharynx, gut, and cells of spinal cord. While receptors of measles virus occur in most tissues.
Differences in nature of polio and measles can be explained through the dissimilarities in the distribution of receptor proteins of host cells to which viruses get adsorbed. In some naked viruses (e.g. adenoviruses) the attachment sites are small fibres at the corners of icosahedron. In enveloped viruses (e.g. myxoviruses) the attachment sites are the spikes present on the surface of envelope.
For example, influenza virus has two types of spikes: H (haemagglutinin) spikes and N (neuraminidase) spikes. The H spikes attach to the host cell receptor site by recognising sialic acid (N-acetyl neuraminic acid), the sugar derivative of glucoprotein.
Influenza neuraminidase helps the virus in penetrating the nasal and respiratory tract secretions by degrading mucosal polysaccharides. However, the receptor sites also vary from person to person.
Stage # 2. Penetration:
Animal viruses penetrate the host cell shortly after adsorption.
Though the detailed mechanism of penetration in not clear, the following three modes are the most favoured by the researchers:
1. Direct penetration:
Some naked animal viruses (e.g., picornaviruses, adenoviruses) use vesicle acidification that causes a major change in capsid structure after adsorption to plasma membrane. This altered capsid contacts the vesicle membrane and either releases the viral genome into the cytoplasm through a membrane pore (picornaviruses) or ruptures the membrane to release the viral genome (adenovirus) into the cytoplasm (Fig. 14.3).
2. Fusion with plasma membrane:
The envelop of enveloped virus (e.g., paramyxoviruses) fuses directly with host plasma membrane. Fusion may involve special envelop fusion proteins that bind to plasma membrane proteins. Finally, the nucleocapsid enters the cytoplasmic matrix where un-coating is done (Fig. 14.4). A virus polymerase associated with the nucleocapsid, transcribes the virus RNA while the latter is still within the capsid.
Many of the enveloped viruses and certain non-enveloped viruses enter the host cell through engulfment by receptor-mediated endocytosis and form coated vesicles.
The virions attach to coated pits with the protein clathrin and the pits then pinch off to form coated vesicles filled with viruses. These vesicles fuse with lysosomes after the clathrin has been removed. Lysosomal enzymes help in un-coating of virion inside the cytoplasm. (Fig. 14.5).
Stage # 3. Un-Coating:
Un-coating is the process of separation of viral genome from the protein coat. Though the process of un-coating is not fully understood, it is proclaimed that the lysosomal enzymes help in animal virus un-coating by degrading the capsid and low endosomal pHs often trigger the process of un-coating.
It has been reported in some cases that the viral envelop fuses with the lysosomal membrane and the partially degraded capsid along with viral genome (nucleocapsid) is released into the host cytoplasm. Once in the cytoplasm, viral genome may be released from the capsid upon completion of un-coating or may function while still attacked to capsid components.
Stage # 4. Replication of Viral Genome:
The replication process of DNA viruses differs from that of RNA viruses. However, in some DNA viruses the replication takes place in cytoplasm (e.g., poxviruses) and in some others in the nucleus of host (e.g., parvoviruses, papovaviruses, adenoviruses, herpes viruses).
Replication of viral genome in RNA viruses is more or less the same as in DNA viruses except the mechanism of formation of mRNA among the different group.
Stage # 5. Synthesis and Assembly of Virus Capsids:
Certain late genes direct the synthesis of capsid proteins. The latter spontaneously self-assemble to form the capsid. It appears that in case of icosahedral viruses the capsid protein assembly first forms procapsid in which the viral genome is inserted by some unknown mechanism. However, in case of enveloped viruses the capsid protein assembly is generally similar to that of naked viruses (poxvirus is exception).
The capsids of these viruses are assembled in the cell cytoplasm by a lengthy, complex procedure that begins with the enclosure of a portion of cytoplasmic matrix through construction of a new membrane. Now the newly synthesized viral DNA condenses, passes through the membrane, and moves to the centre of the immature virus.
Stage # 6. Release of New Virus:
Release of newly formed animal viruses from the host cell differs between naked and enveloped viruses. The naked animal viruses are released most often by the lysis of the host cell. In enveloped viruses, however, the virus-encoded proteins are incorporated in the plasma membrane and then the nucleocapsid is simultaneously released; the envelop is formed by membrane-budding.