Viruses - What intracellular processes are involved in viral replication?
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 sialic acid-rich glycoproteins, proteoglycans such as HSPG, receptors such
as the LDL and CD4 receptor, or proteins that form tight junctions such as occludins and
claudins. If the virion possesses an envelope, it fuses
with the plasma membrane after attachment to the membrane protein and releases the capsid
into the hosts’ 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 capsid 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 capsid 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 IRES. 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 the 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 cell’s
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.