- Viral replication
Viral replication is the term used by
virologists to describe the formation of biological viruses during the infection process in the target host cells. Viruses must first get into the cell before viral replication can occur. From the perspective of the virus, the purpose of viral replication is to allow production and survival of its kind. By generating abundant copies of its genomeand packaging these copies into viruses, the virus is able to continue infecting new hosts. Replication between viruses is greatly varied and depends on the type of genes involved.
Baltimore Classification System
Viruses are classed into 7 types of genes, each of which have their own families of viruses, which in turn have differing replication strategies themselves.
David Baltimore, a Nobel Prize-winning biologist, devised a system called the Baltimore Classification Systemto classify different viruses based on their unique replication strategy. There are seven different replication strategies based on this system (Baltimore Class I, II, III, IV, V, VI, VII). The seven classes of viruses are listed here briefly and in generalities [N.J. Dimmock et al. "Introduction to Modern Virology, 6th edition." Blackwell Publishing, 2007.] .
Class 1: Double stranded DNA viruses
This type of virus usually must enter the host nucleus before it is able to replicate. Furthermore, these viruses require host cell polymerases to replicate its
genomeand hence is highly dependent on the cell cycle. Proper infection and production of progeny requires that the cell be in replication as that is when the cell's polymerases are active. The virus may induce the cell to forcefully undergo cell division, and chronically, this may lead to transformation of the cell and ultimately, cancer. An example of a family within this classification is the Adenoviridae.
There is only one well studied example in which a class 1 virus is not replicating within the nucleus, that is the
Poxvirusfamily, a highly pathogenic virus that infects vertebrates. The example is a smallpoxvirus.
Class 2: Single stranded DNA viruses
Viruses that fall under this category includes ones that are not as well studied, but still do pertain highly to vertebrates. Two examples include the
Circoviridaeand Parvoviridae. They replicate within the nucleus, and form a double stranded DNA intermediate during replication. A human Circovirus called TTVis included within this classification and is found in most all humans, infecting them asymptomatically in nearly every major organ.
Class 3: Double stranded RNA viruses
As with most
RNAviruses, this class replicates in the cytoplasm, not having to use the host replication polymerases to as much a degree as DNAviruses. This family is also not as well studied as the rest and includes 2 major families, the Reoviridaeand Birnaviridae. Replication is monocistronicand includes individual, segmented genomes, meaning that each of the genes code for only one protein, unlike other viruses which exhibit more complex translation.
Class 4 & 5: Single stranded RNA viruses
These viruses consist of two types, however both share the fact that replication is primarily in the cytoplasm, and that replication is not as dependent on the cell cycle as DNA viruses. This class of viruses are also one of the best well studied, alongside the double stranded DNA viruses.
Class 4: Single stranded RNA viruses - Positive (+) sense
The positive sense RNA viruses and indeed all genes defined as
positive sensecan be directly accessed by host polymerases to immediately form proteins. These can be divided into two groups, both of which reproduce in the cytoplasm:
* Viruses with
polycistronic mRNAwhere the genome RNA forms the mRNA and is translated into a polyproteinproduct that is subsequently cleaved to form the mature proteins. This means that the gene can utilize a few methods in which to produce proteins from the same strand of RNA, all in the sake of reducing the size of its gene.
* Viruses with complex transcription, for which
subgenomicmRNAs, ribosomal frameshiftingand proteolyticprocessing of polyproteins may be used. All of which are different mechanisms with which to produce proteins from the same strand of RNA.
Examples of this class include the families
Coronaviridae, Flaviviridaeand Picornaviridae.
Class 5: Single stranded RNA viruses - Negative (-) sense
The negative sense RNA viruses and indeed all genes defined as
negative sensecannot be directly accessed by host polymerases to immediately form proteins. Instead, they must be transcripted by viral polymerases into a "readable" form, which is the positive sense reciprocal. These can also be divided into two groups:
* Viruses containing non segmented
genomesfor which the first step in replication is transcription from the (-) stranded genome by the viral RNA-dependent RNA polymerase to yield monocistronic mRNAs that code for the various viral proteins. A (+) sense genome copy is then produced that serves as template for production of the (-) strand genome. Replication is within the cytoplasm.
* Viruses with segmented genomes for which replication occurs in the nucleus and for which the viral RNA-dependent RNA polymerase produces monocistronic mRNAs from each genome segment. The largest difference between the two is the location of replication.
Examples in this class include the families
Orthomyxoviridae, Paramyxoviridae, Bunyaviridae, Filoviridaeand Rhabdoviridae(which includes rabies).
Class 6: Positive (+) sense single stranded RNA viruses that replicate through a DNA intermediate
A well studied family of this class of viruses include the
retroviruses. One defining feature is the use of reverse transcriptaseto convert the positive sense RNA into DNA. Instead of using the RNA for templates of proteins, they use DNA to create the templates, which is spliced into the host genome using integrase. Replication can then commence with the help of the host cell's polymerases. A well studied example includes HIV.
Class 7: Double stranded DNA viruses that replicate through a single stranded RNA intermediate
This small group of viruses, exemplified by the
Hepatitis Bvirus, have a double-stranded, gapped genome that is subsequently filled in to form a covalently closed circle ( ccc DNA) that serves as a template for production of viral mRNAs and a subgenomicRNA. The pregenome RNA serves as template for the viral reverse transcriptase and for production of the DNA genome.
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