Viral replication is the formation of biological
virus
A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea.
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es during the infection process in the target host cells. Viruses must first get into the cell before viral replication can occur. Through the generation of abundant copies of its
genome
In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ...
and packaging these copies, the virus continues infecting new hosts. Replication between viruses is greatly varied and depends on the type of genes involved in them. Most DNA viruses assemble in the nucleus while most RNA viruses develop solely in cytoplasm.
Viral production / replication
Viruses multiply only in living cells. The
host cell must
provide the
energy
In physics, energy (from Ancient Greek: ἐνέργεια, ''enérgeia'', “activity”) is the quantitative property that is transferred to a body or to a physical system, recognizable in the performance of work and in the form of ...
and synthetic machinery and the low-
molecular-weight precursors for the synthesis of viral proteins and nucleic acids.
The virus replication occurs in seven stages, namely;
# Attachment
# Entry,
# Uncoating,
#
Transcription /
mRNA
In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of synthesizing a protein.
mRNA is created during the ...
production,
# Synthesis of
virus
A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea.
Since Dmitri Ivanovsk ...
components,
#
Virion assembly and
#
Release (Liberation Stage).
Attachment
It is the first step of viral replication. The virus attaches to the
cell membrane
The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (t ...
of the host
cell. It then injects its
DNA or
RNA into the host to initiate infection.
In animal cells these viruses get into the cell through the process of
endocytosis which works through fusing of the virus and fusing of the
viral envelope with the cell membrane of the animal cell and in plant cells it enters through the process of
pinocytosis which works on pinching of the viruses.
Entry
The cell membrane of the host cell invaginates the virus particle, enclosing it in a
pinocytotic vacuole
A vacuole () is a membrane-bound organelle which is present in plant and fungal cells and some protist, animal, and bacterial cells. Vacuoles are essentially enclosed compartments which are filled with water containing inorganic and organic m ...
. This protects the cell from
antibodies
An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of ...
like in the case of the
HIV virus.
Uncoating
Cell
enzymes (from
lysosomes) strip off the virus
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
coat.
This releases or renders accessible the virus nucleic acid or
genome
In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ...
.
Transcription / mRNA production
For some
RNA viruses, the infecting RNA produces messenger RNA (
mRNA
In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of synthesizing a protein.
mRNA is created during the ...
), which can translate the genome into protein products.
For viruses with negative stranded RNA, or DNA, viruses are produced by
transcription then translation.
The mRNA is used to instruct the host cell to make virus components. The virus takes advantage of the existing cell structures to replicate itself.
Synthesis of virus components
The components are manufactured by the virus using the host's existing
organelles:
* Viral proteins: Viral mRNA is translated on cellular
ribosomes into two types of viral protein:
** Structural: proteins which make up the virus particle
** Nonstructural: proteins not found in the virus particle, mainly enzymes for virus genome replication
* Viral nucleic acid (genome replication): New viral genomes are synthesized; templates are either the parental genome or newly formed complementary strands, in the case of single-stranded genomes. These genomes are made by either a viral
polymerase or (in some DNA viruses) a cellular enzyme, particularly in rapidly dividing cells.
Virion assembly
A
virion is simply an active or intact virus particle. In this stage, newly synthesized genome (nucleic acid), and proteins are assembled to form new virus particles.
This may take place in the cell's nucleus,
cytoplasm
In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. ...
, or at
plasma membrane for most developed viruses.
Release (liberation stage)
The viruses, now being matured are released by either sudden rupture of the cell, or gradual extrusion (force out) of enveloped viruses through the
cell membrane
The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (t ...
.
The new viruses may invade or attack other cells, or remain
dormant in the cell.
In the case of bacterial viruses, the release of progeny virions takes place by
lysis
Lysis ( ) is the breaking down of the membrane of a cell, often by viral, enzymic, or osmotic (that is, "lytic" ) mechanisms that compromise its integrity. A fluid containing the contents of lysed cells is called a ''lysate''. In molecular b ...
of the infected bacterium. However, in the case of animal viruses, release usually occurs without cell lysis.
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 (born March 7, 1938) is an American biologist, university administrator, and 1975 Nobel laureate in Physiology or Medicine. He is President Emeritus and Distinguished Professor of Biology at the California Institute of Tec ...
, a
Nobel Prize
The Nobel Prizes ( ; sv, Nobelpriset ; no, Nobelprisen ) are five separate prizes that, according to Alfred Nobel's will of 1895, are awarded to "those who, during the preceding year, have conferred the greatest benefit to humankind." Alfr ...
-winning biologist, devised a system called the
Baltimore Classification System
Baltimore classification is a system used to classify viruses based on their manner of messenger RNA (mRNA) synthesis. By organizing viruses based on their manner of mRNA production, it is possible to study viruses that behave similarly as a d ...
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.
[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
Nucleus ( : nuclei) is a Latin word for the seed inside a fruit. It most often refers to:
* Atomic nucleus, the very dense central region of an atom
*Cell nucleus, a central organelle of a eukaryotic cell, containing most of the cell's DNA
Nucl ...
before it is able to replicate. Some of these viruses require host cell
polymerases to replicate their
genome
In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ...
, 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
The cell cycle, or cell-division cycle, is the series of events that take place in a cell that cause it to divide into two daughter cells. These events include the duplication of its DNA (DNA replication) and some of its organelles, and sub ...
. The virus may induce the cell to forcefully undergo
cell division
Cell division is the process by which a parent cell divides into two daughter cells. Cell division usually occurs as part of a larger cell cycle in which the cell grows and replicates its chromosome(s) before dividing. In eukaryotes, there ...
, which may lead to
transformation of the cell and, ultimately,
cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
. An example of a family within this classification is the
Adenoviridae
Adenoviruses (members of the family ''Adenoviridae'') are medium-sized (90–100 nm), nonenveloped (without an outer lipid bilayer) viruses with an icosahedral nucleocapsid containing a double-stranded DNA genome. Their name derives from thei ...
.
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
Vertebrates () comprise all animal taxa within the subphylum Vertebrata () ( chordates with backbones), including all mammals, birds, reptiles, amphibians, and fish. Vertebrates represent the overwhelming majority of the phylum Chordata, with ...
s.
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'' is a family of DNA viruses. Birds and mammals serve as natural hosts. There are 101 species in this family, assigned to 2 genera. Diseases associated with this family include: PCV-2: postweaning multisystemic wasting syndrome; ...
and
Parvoviridae. They replicate within the nucleus, and form a double-stranded DNA intermediate during replication. A human Anellovirus called
TTV is included within this classification and is found in almost all humans, infecting them
asymptomatically in nearly every major
organ
Organ may refer to:
Biology
* Organ (biology), a part of an organism
Musical instruments
* Organ (music), a family of keyboard musical instruments characterized by sustained tone
** Electronic organ, an electronic keyboard instrument
** Hammond ...
.
Class 3: Double-stranded RNA viruses
Like most viruses with
RNA genomes, double-stranded RNA viruses do not rely on host polymerases for replication to the extent that viruses with
DNA genomes do. Double-stranded RNA viruses are not as well-studied as other classes. This class includes two major families, the
Reoviridae and
Birnaviridae. Replication is
monocistronic
A cistron is an alternative term for "gene". The word cistron is used to emphasize that genes exhibit a specific behavior in a cis-trans test; distinct positions (or loci) within a genome are cistronic.
History
The words ''cistron'' and ''gene ...
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 replicate in the cytoplasm:
* Viruses with
polycistronic
A cistron is an alternative term for " gene". The word cistron is used to emphasize that genes exhibit a specific behavior in a cis-trans test; distinct positions (or loci) within a genome are cistronic.
History
The words ''cistron'' and ''ge ...
mRNA
In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of synthesizing a protein.
mRNA is created during the ...
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, reducing the size of its genome.
* Viruses with complex transcription, for which
subgenomic
Subgenomic mRNAs are essentially smaller sections of the original transcribed template strand.
3' to 5' DNA or RNA
During transcription, the original template strand is usually read from the 3' to the 5' end from beginning to end. Subgenomic ...
mRNAs,
ribosomal frameshifting and
proteolytic
Proteolysis is the breakdown of proteins into smaller polypeptides or amino acids. Uncatalysed, the hydrolysis of peptide bonds is extremely slow, taking hundreds of years. Proteolysis is typically catalysed by cellular enzymes called prote ...
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
Picornaviruses are a group of related nonenveloped RNA viruses which infect vertebrates including fish, mammals, and birds. They are viruses that represent a large family of small, positive-sense, single-stranded RNA viruses with a 30 ...
.
Class 5: Single-stranded RNA viruses - negative-sense
The negative-sense RNA viruses and indeed all genes defined as
negative-sense
In molecular biology and genetics, the sense of a nucleic acid molecule, particularly of a strand of DNA or RNA, refers to the nature of the roles of the strand and its complement in specifying a sequence of amino acids. Depending on the context, ...
cannot be directly accessed by host ribosomes to immediately form proteins. Instead, they must be
transcribed 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 cytoplasm and for which the viral RNA-dependent RNA polymerase produces monocistronic mRNAs from each genome segment.
Examples in this class include the families
Orthomyxoviridae,
Paramyxoviridae,
Bunyaviridae,
Filoviridae, and
Rhabdoviridae
''Rhabdoviridae'' is a family of negative-strand RNA viruses in the order '' Mononegavirales''. Vertebrates (including mammals and humans), invertebrates, plants, fungi and protozoans serve as natural hosts. Diseases associated with member ...
(which includes
rabies
Rabies is a viral disease that causes encephalitis in humans and other mammals. Early symptoms can include fever and tingling at the site of exposure. These symptoms are followed by one or more of the following symptoms: nausea, vomiting, ...
).
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 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.
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 (
cccDNA) that serves as a template for production of viral
mRNA
In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of synthesizing a protein.
mRNA is created during the ...
s and a
subgenomic
Subgenomic mRNAs are essentially smaller sections of the original transcribed template strand.
3' to 5' DNA or RNA
During transcription, the original template strand is usually read from the 3' to the 5' end from beginning to end. Subgenomic ...
RNA. The pregenome RNA serves as template for the viral reverse transcriptase and for production of the DNA genome.
References
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Viruses
Virology
Viral life cycle