[0:11]Viruses. What intracellular processes are involved in viral replication?
[0:19]Viruses are transferred as particles known as virions. Once the virion enters a host cell, it disassembles and the viral genome begins to interfere with cellular processes. The first stage of the intracellular phase of the viral replication cycle is cell entry. Viruses are unable to diffuse across biological membranes, therefore they infect host cells with membrane proteins that facilitate virus attachment. Viral membrane proteins facilitating entry include sic acid rich glycoproteins, proteoglycans such as HSPG, receptors such as the LDL and CD4 receptor, or proteins that form tight junctions such as oculins and claudins. If the virion possesses an envelope, it fuses with the plasma membrane after attachment to the membrane protein and releases the capside into the host cytoplasm. For other viruses, especially non-enveloped viruses, virions can be endocytosed upon receptor binding. In the cytoplasm, virions are transported along the cytoskeletal filaments. The genome of RNA viruses is usually required to enter the host cell cytoplasm. This is ensured by a process termed uncoating, whereby the viral capsd is taken apart. Virus uncoating is initiated by different triggers. They usually take advantage of the endosomal pH, which gradually becomes more acidic. This alters the shape of the capset proteins, thereby destabilizing viral assembly, resulting in its disassembly and genome release. Now back to the RNA released in the cytoplasm. If required, viral RNA is transformed into messenger RNA, followed by the start of viral protein translation. The viral mRNA strand contains enough genetic information to encode several proteins. This can be achieved by, for example, specific MRNA folding patterns, which serve as initial ribosome entry sites, in short, IRS. They enable for translation initiation to commence in the middle of an MRNA strand. The coding capacity of an MRNA strand can also be increased by splitting the translated peptide chain into several entities, which fold into separate functional proteins. The first viral proteins to be translated are those involved in replication processes and are often referred to as early proteins. They are mainly catalytically active and therefore synthesized in smaller amounts. Structural proteins required to form new capsids are subsequently produced and hence accordingly named late proteins. These proteins need to be produced in large quantities. Once RNA replication and protein production have yielded a sufficient amount of viral components, self-assembly into a new virion takes place. There are three different pathways involved in the release of new virions. Particles travel through the endoplasmic reticulum and Golgi apparatus in order to undergo exocytosis. Inside the different cell compartments, the viral particles often undergo pH dependent maturation. Another mechanism often observed is the release of viruses by budding. Viral proteins are incorporated into the host membrane, which the virion later acquires as its final envelope. This membrane is either a compartment such as for the endoplasmic reticulum or Golgi apparatus, or the plasma membrane as shown in the image here. During this process, viral components usually assemble directly at the budding site. Most non-enveloped viruses are released through a third pathway, cell lysis. The virus disrupts the plasma membrane, invariably killing the host cell. Now let's take a look at DNA viruses. There are many similarities between the replication cycle of RNA and DNA viruses. However, there is one major difference. The genome of DNA viruses needs to be delivered into the host nucleus to take advantage of the cells existing transcriptional machinery. Therefore, virion uncoating is accompanied or followed by nuclear import. Inside the nucleus, some viral DNA may initially require transformation into positive sense double stranded DNA in order to be transcribed. Transcription produces mRNA, which is treated like regular host mRNA and travels to the cytoplasm for translation. DNA replication also occurs in the cell's nucleus, using mostly cellular proteins. To assemble new viral particles, viral structural proteins are transported into the nucleus where they self-assemble. The virions then penetrate the nuclear membrane by vesicle formation and are subsequently released from the cell. These particles can now be transmitted to other cells or organisms.
