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 genome and 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.

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Baltimore Classification System

Main article: 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 System to 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^[1].

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 genome and 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 Poxvirus family, a highly pathinogenic virus that infects vertebrates and includes the smallpox virus.

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 Circoviridae and Parvoviridae. They replicate within the nucleus, and form a double stranded DNA intermediate during replication. A human Circovirus called TTV is 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 RNA viruses, this class replicates in the cytoplasm, not having to use the host replication polymerases to as much a degree as DNA viruses. This family is also not as well studied as the rest and includes 2 major families, the Reoviridae and Birnaviridae. Replication is monocistronic and 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 other 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 sense can 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 mRNA where the genome RNA forms the mRNA and is translated into a polyprotein product 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 subgenomic mRNAs, ribosomal frameshifting and proteolytic processing 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, Flaviviridae and Picornaviridae.

Class 5: Single stranded RNA viruses - Negative (-) sense

The negative sense RNA viruses and indeed all genes defined as negative sense cannot 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 genomes for 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, Filoviridae and 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 transcriptase to convert the positive sense RNA into DNA. Instead of using the RNA for templates of proteins, they in instead converted into DNA and 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 though a single stranded RNA intermediate

This small group of viruses, exemplified by the Hepatitis B virus, 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 subgenomic RNA. The pregenome RNA serves as template for the viral reverse transcriptase and for production of the DNA genome.

Aftermath

After replication of the virus has occurred, the virus will generally exhaust all the cellular resources, leading to cell death and the next step of the viral life cycle: viral shedding. However, a virus may choose, depending on the virus and environment, to instead become dormant within the cell, to emerge later. This would be deemed as: viral latency.

References

1. ^ N.J. Dimmock et al. "Introduction to Modern Virology, 6th edition." Blackwell Publishing, 2007.