Viral replication
Encyclopedia
Viral replication is the term used by virologists to describe the formation of biological virus
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...

es 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
Genome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....

 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 in them. Most DNA viruses assemble in nucleus while most RNA viruses develop solely in cytoplasm. .

Baltimore Classification System

Viruses are classed into 7 types of genes, each of which has its own families of viruses, which in turn have differing replication strategies themselves. David Baltimore
David Baltimore
David Baltimore is an American biologist, university administrator, and Nobel laureate in Physiology or Medicine. He served as president of the California Institute of Technology from 1997 to 2006, and is currently the Robert A. Millikan Professor of Biology at Caltech...

, a Nobel Prize
Nobel Prize
The Nobel Prizes are annual international awards bestowed by Scandinavian committees in recognition of cultural and scientific advances. The will of the Swedish chemist Alfred Nobel, the inventor of dynamite, established the prizes in 1895...

-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.

Class 1: Double-stranded DNA viruses

This type of virus usually must enter the host nucleus
Cell nucleus
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...

 before it is able to replicate. Some of these viruses require host cell polymerases
DNA polymerase
A DNA polymerase is an enzyme that helps catalyze in the polymerization of deoxyribonucleotides into a DNA strand. DNA polymerases are best known for their feedback role in DNA replication, in which the polymerase "reads" an intact DNA strand as a template and uses it to synthesize the new strand....

 to replicate their genome
Genome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....

, while others, such as adenoviruses or herpes viruses, encode their own replication factors. However, in either cases, replication of the viral genome is highly dependent on a cellular state permissive to DNA replication and, thus, on the cell cycle
Cell cycle
The cell cycle, or cell-division cycle, is the series of events that takes place in a cell leading to its division and duplication . In cells without a nucleus , the cell cycle occurs via a process termed binary fission...

. The virus may induce the cell to forcefully undergo cell division
Cell division
Cell division is the process by which a parent cell divides into two or more daughter cells . Cell division is usually a small segment of a larger cell cycle. This type of cell division in eukaryotes is known as mitosis, and leaves the daughter cell capable of dividing again. The corresponding sort...

, which may lead to transformation of the cell and, ultimately, cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

. An example of a family within this classification is the Adenoviridae
Adenoviridae
Adenoviruses are medium-sized , nonenveloped icosahedral viruses composed of a nucleocapsid and a double-stranded linear DNA genome...

.

There is only one well-studied example in which a class 1 family of viruses does not replicate within the nucleus. This is the Poxvirus family, which comprises highly pathogenic viruses that infect vertebrate
Vertebrate
Vertebrates are animals that are members of the subphylum Vertebrata . Vertebrates are the largest group of chordates, with currently about 58,000 species described. Vertebrates include the jawless fishes, bony fishes, sharks and rays, amphibians, reptiles, mammals, and birds...

s. One example is the smallpox
Smallpox
Smallpox was an infectious disease unique to humans, caused by either of two virus variants, Variola major and Variola minor. The disease is also known by the Latin names Variola or Variola vera, which is a derivative of the Latin varius, meaning "spotted", or varus, meaning "pimple"...

 virus.

Class 2: Single-stranded DNA viruses

Viruses that fall under this category include ones that are not as well-studied, but still do pertain highly to vertebrates. Two examples include the Circoviridae
Circoviridae
The Circoviridae are a family of viruses. These are small, relatively poorly-studied viruses, with circular, single-stranded DNA genomes of approximately one to four kilobases-Virology:...

 and Parvoviridae
Parvoviridae
The Parvoviridae family includes the smallest known viruses, and some of the most environmentally resistant. They were discovered during the 1960s and affect vertebrates and insects...

. They replicate within the nucleus, and form a double-stranded DNA intermediate during replication. A human Circovirus called TTV
Transfusion Transmitted Virus
TT virus was the first member of the new family Anelloviridae to be discovered.- Initial discovery :TTV, for Transfusion Transmitted Virus or Torque teno virus was first reported in a Japanese patient in 1997 by the research scientist T. Nishizawa...

 is included within this classification and is found in almost all humans, infecting them asymptomatic
Asymptomatic
In medicine, a disease is considered asymptomatic if a patient is a carrier for a disease or infection but experiences no symptoms. A condition might be asymptomatic if it fails to show the noticeable symptoms with which it is usually associated. Asymptomatic infections are also called subclinical...

ally in nearly every major organ.

Class 3: Double-stranded RNA viruses

Like most viruses with RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....

 genomes, double-stranded RNA viruses do not rely on host polymerases for replication to the extent that viruses with DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

 genomes do. Double-stranded RNA viruses are not as well-studied as other classes. This class includes two major families, the Reoviridae
Reoviridae
Reoviridae is a family of viruses that can affect the gastrointestinal system and respiratory tract. Viruses in the family Reoviridae have genomes consisting of segmented, double-stranded RNA...

 and Birnaviridae
Birnaviridae
The birnaviridae are a family of viruses, including the following genera:*Genus Aquabirnavirus; type species: Infectious pancreatic necrosis virus*Genus Avibirnavirus; type species: Infectious bursal disease virus...

. Replication is monocistronic and includes individual, segmented genomes, meaning that each of the genes codes for only one protein, unlike other viruses, which exhibit more complex translation.

Classes 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 that of DNA viruses. This class of viruses is also one of the most-studied types of viruses, 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 ribosomes 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
Coronaviridae
Coronaviruses are enveloped, single-stranded, positive-sense RNA viruses with club-shaped surface about 120-160 nm in diameter that resemble a “corona”.-Virology:...

, Flaviviridae
Flaviviridae
The Flaviviridae are a family of viruses that are primarily spread through arthropod vectors . The family gets its name from Yellow Fever virus, a type virus of Flaviviridae; flavus means yellow in Latin...

, 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 transcribed
Transcription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...

 by viral polymerases into the "readable" complementary positive-sense. These can also be divided into two groups:
  • Viruses containing nonsegmented genomes for which the first step in replication is transcription from the negative-stranded genome by the viral RNA-dependent RNA polymerase to yield monocistronic mRNAs that code for the various viral proteins. A positive-sense genome copy that serves as template for production of the negative-strand genome is then produced. Replication is within the cytoplasm.
  • Viruses with segmented genomes for which replication occurs in the nucleus
    Cell nucleus
    In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...

     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
Orthomyxoviridae
The Orthomyxoviridae are a family of RNA viruses that includes five genera: Influenzavirus A, Influenzavirus B, Influenzavirus C, Isavirus and Thogotovirus. A sixth has recently been described...

, Paramyxoviridae, Bunyaviridae
Bunyaviridae
Bunyaviridae is a family of negative-stranded RNA viruses. Though generally found in arthropods or rodents, certain viruses in this family occasionally infect humans. Some of them also infect plants....

, Filoviridae
Filoviridae
The family Filoviridae is the taxonomic home of several related viruses that form filamentous virions. Two members of the family that are commonly known are Ebola virus and Marburg virus. Both viruses, and some of their lesser known relatives, cause severe disease in humans and nonhuman primates in...

, and Rhabdoviridae
Rhabdoviridae
Rhabdoviruses are viruses belonging to the family Rhabdoviridae, which is in the order Mononegavirales. The name is derived from the Greek rhabdos meaning rod referring to the shape of the viral particles. Rhabdoviruses infect a broad range of hosts throughout the animal and plant kingdoms...

 (which includes rabies
Rabies
Rabies is a viral disease that causes acute encephalitis in warm-blooded animals. It is zoonotic , most commonly by a bite from an infected animal. For a human, rabies is almost invariably fatal if post-exposure prophylaxis is not administered prior to the onset of severe symptoms...

).

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
Reverse transcriptase
In the fields of molecular biology and biochemistry, a reverse transcriptase, also known as RNA-dependent DNA polymerase, is a DNA polymerase enzyme that transcribes single-stranded RNA into single-stranded DNA. It also helps in the formation of a double helix DNA once the RNA has been reverse...

 to 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
Integrase
Retroviral integrase is an enzyme produced by a retrovirus that enables its genetic material to be integrated into the DNA of the infected cell...

. Replication can then commence with the help of the host cell's polymerases. A well-studied example includes HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...

.

Class 7: Double-stranded DNA viruses that replicate through 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.
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