Viral Replication & Genetics
Overview
Virus particles, aka, virions, comprise components that self-assemble.
Thus, virions do not replicate via fission or division, like bacterial and eukaryotic cells do.
We'll show viral replication in the following steps:
1. Adhesion
2. Entry
3. Uncoating
4. Synthesis and Assembly
5. Virion release.
ADHESION
Attachment proteins on the surface of the virion binds with host cell adhesion receptors.
A range of host cell surface proteins can act as virion receptors.
For example, the
Epstein-Barr virus attaches to specific complement receptors on B cells.
Tissue tropism occurs when a virus's attachment proteins interact only with receptors on specific cell types.
For example, the
rabies virus interacts with acetylcholine receptors on neurons, so it is a neurotropic virus.
ENTRY
The virion moves along the host cell surface, where it can encounter entry receptors, aka, co-receptors that facilitate movement into the cell.
HIV virions, for example, bind with chemokine receptors that trigger conformational changes and facilitate entry into the host cell.
Entry can occur via endocytosis or membrane fusion.
Enveloped viruses often enter host cells via membrane fusion.
UNCOATING
Uncoating is a highly variable process that disassembles virions to expose their nucleic acids for replication.
SYNTHESIS & ASSEMBLY
These processes vary according to the type of nucleic acids present.
DNA viruses
DNA viruses move to the nucleus for genome replication (poxviruses are an exception)
1. Immediate-early and early transcription produces the enzymes and proteins needed for late transcription.
2. Early transcription is followed by genome replication.
3. Late transcription produces the capsid structural proteins.
4. Assembly results in the formation of the nucleocapsid.
RNA viruses
Most RNA viruses replicate in the cytoplasm (exceptions include influenza and
retroviruses).
Positive-sense strand viral genomes act as mRNA for protein synthesis, so translation can begin immediately.
Naked positive-sense viral genomes are infectious.
Negative-sense strand viral genomes do not immediately begin transcription.
Act as a template for synthesis of a positive-sense strand, which is then used for protein synthesis.
Naked negative-sense strand viral genomes are not infectious by themselves.
The RNA virus genome encodes RNA-dependent RNA polymerases as well as the enzymes necessary for viral mRNA processing.
Self-assembly of the genome and structural proteins produces the nucleocapsid.
RELEASE
Budding
Process by which a nucleocapsid acquires a lipid envelope by passing through Golgi, nuclear, or cytoplasmic cell membranes.
Exocytosis
Reverse phagocytosis.
Cell lysis
Naked capsids are often released via lysis.
Products of virion release
Noninfectious, defective virions
Infectious particles = Burst Size
Interferon release
Interferons are cytokines that prevent viral replication, induce T-cell recruitment.
Cytotoxic T cells
Kill the virally-infected cells, and antibodies can remove viruses before they infect cells.
Recombination
Genetic information is exchanged between viruses or a virus and its host.
Reassortment
Viruses with segmented genomes create a hybrid strain.
This can lead to antigenic shift.
An example of this is the H1N1 pandemic strain that arose in 2009; this strain contained genetic information from avian, human, and swine influenza viruses.
Complementation
Gene products or functions of a mutated virus are complemented by another virus.
In other words, a mutated virus is non-functional until its complement virus arrives and produces a protein or function that is beneficial to both.
For example, Hepatitis D relies on replicating Hepatitis B to provide its envelope protein.
Phenotypic mixing
A virus genome is partially or completely coated with surface proteins of a different virus.
Be aware that the progeny of this virion will have a protein coat that matches its genome.