Dependovirus
Encyclopedia
Dependovirus is a genus of the Parvoviridae
virus
es, which are Group II viruses according to the Baltimore classification
. The Dependovirus is part of the sub family
of the Parvoviridae family
known as the Parvovirinae. Dependovirus is also known as Adeno-associated virus because Dependovirus cannot replicate
and form viral capsid
s in its host cell
without the cell being coinfected
by a helper virus
such as an adenovirus
, a herpesvirus
, or a vaccinia virus
.
The genome is a single molecule of single stranded with a length of 4.7 kilobases. It has only two open reading frames. The 3' open reading frame is the structural capsid protein, cap, which can be spliced to form two RNAs, one for virion protein 1 (VP1) and the other goes on to eventually make VP2 and VP3. The second gene, rep, can be spliced into four different, nonstructural, regulatory proteins that all aid in the genome replication. These proteins are named Rep 78, Rep68, Rep 52, and Rep 40 based on their molecular weight.
Due to inverted, complementary long terminal repeats (LTRs) at each end of the genome, a T shaped secondary structure
is formed. The complementary areas leave a 3’ hydroxyl
group single stranded for the replication to begin. This 3’ hydroxyl group is used as a primer
for the leading strand synthesis. Both positive and negative sense strands of DNA are made. Double stranded intermediates are formed throughout the replication; this means the two strands, positive and negative sense, will be matched up..
is a possible treatment for a variety of disorders and diseases that are genetic in origin. Viral vectors are currently being developed to transport genes into human cells. Since this virus does not stimulate an immune response it can be used multiple times effectively without being neutralized before infection. Another reason these viruses are reliable vectors is the known insertion point for the genome. This virus always inserts its contents into the same place on chromosome 19. This predictability can cut down on the chances of inserting into an important area that might disrupt normal gene function or increase the risk of developing cancer.
At this time, one challenge using this virus as a therapy tool is the fact that the genome is fairly small. With less than 5kb in the genome the amount of genetic material that can fit into the capsid is limited. Work is currently being done to increase the amount of information this vector can deliver. This may be accomplished by the LTRs found at both the 5’ and 3’ end of the genome. Since the LTRs have the same sequence they will leave complementary strands exposed if they are removed. The complementary strands can undergo recombination
and join two 5kb inserted fragments together.
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...
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, which are Group II viruses according to the Baltimore classification
Baltimore classification
The Baltimore classification, developed by David Baltimore, is a virus classification system that groups viruses into families, depending on their type of genome and their method of replication....
. The Dependovirus is part of the sub family
Family (biology)
In biological classification, family is* a taxonomic rank. Other well-known ranks are life, domain, kingdom, phylum, class, order, genus, and species, with family fitting between order and genus. As for the other well-known ranks, there is the option of an immediately lower rank, indicated by the...
of the Parvoviridae family
Family (biology)
In biological classification, family is* a taxonomic rank. Other well-known ranks are life, domain, kingdom, phylum, class, order, genus, and species, with family fitting between order and genus. As for the other well-known ranks, there is the option of an immediately lower rank, indicated by the...
known as the Parvovirinae. Dependovirus is also known as Adeno-associated virus because Dependovirus cannot replicate
DNA replication
DNA replication is a biological process that occurs in all living organisms and copies their DNA; it is the basis for biological inheritance. The process starts with one double-stranded DNA molecule and produces two identical copies of the molecule...
and form viral capsid
Capsid
A capsid is the protein shell of a virus. It consists of several oligomeric structural subunits made of protein called protomers. The observable 3-dimensional morphological subunits, which may or may not correspond to individual proteins, are called capsomeres. The capsid encloses the genetic...
s in its host cell
Host (biology)
In biology, a host is an organism that harbors a parasite, or a mutual or commensal symbiont, typically providing nourishment and shelter. In botany, a host plant is one that supplies food resources and substrate for certain insects or other fauna...
without the cell being coinfected
Coinfection
In parasitology, coinfection is the term used to describe the simultaneous infection of a host by multiple pathogen species. In virology, coinfection can also refer to the simultaneous infection of a single cell by two or more virus particles...
by a helper virus
Helper virus
A helper virus is a virus used when producing copies of a helper dependent viral vector which does not have the ability to replicate on its own. The helper virus is used to coinfect cells alongside the viral vector and provides the necessary enzymes for replication of the genome of the viral vector....
such as an adenovirus
Adenoviridae
Adenoviruses are medium-sized , nonenveloped icosahedral viruses composed of a nucleocapsid and a double-stranded linear DNA genome...
, a herpesvirus
Herpesviridae
The Herpesviridae are a large family of DNA viruses that cause diseases in animals, including humans. The members of this family are also known as herpesviruses. The family name is derived from the Greek word herpein , referring to the latent, recurring infections typical of this group of viruses...
, or a vaccinia virus
Vaccinia
Vaccinia virus is a large, complex, enveloped virus belonging to the poxvirus family. It has a linear, double-stranded DNA genome approximately 190 kbp in length, and which encodes for approximately 250 genes. The dimensions of the virion are roughly 360 × 270 × 250 nm, with a mass of...
.
Virology
The Dependoviruses have and icosahedral shape, measure 22 nm is composed of 60 wedge shaped proteins triangulation number = 1). Three proteins (VP1, VP2 and VP3) are present in each capsomere. Each capsid is made from 5 VP1, 5 VP2, and 50 VP3 proteins. The capsid does not have an envelope.The genome is a single molecule of single stranded with a length of 4.7 kilobases. It has only two open reading frames. The 3' open reading frame is the structural capsid protein, cap, which can be spliced to form two RNAs, one for virion protein 1 (VP1) and the other goes on to eventually make VP2 and VP3. The second gene, rep, can be spliced into four different, nonstructural, regulatory proteins that all aid in the genome replication. These proteins are named Rep 78, Rep68, Rep 52, and Rep 40 based on their molecular weight.
Due to inverted, complementary long terminal repeats (LTRs) at each end of the genome, a T shaped secondary structure
Secondary structure
In biochemistry and structural biology, secondary structure is the general three-dimensional form of local segments of biopolymers such as proteins and nucleic acids...
is formed. The complementary areas leave a 3’ hydroxyl
Hydroxyl
A hydroxyl is a chemical group containing an oxygen atom covalently bonded with a hydrogen atom. In inorganic chemistry, the hydroxyl group is known as the hydroxide ion, and scientists and reference works generally use these different terms though they refer to the same chemical structure in...
group single stranded for the replication to begin. This 3’ hydroxyl group is used as a primer
Primer (molecular biology)
A primer is a strand of nucleic acid that serves as a starting point for DNA synthesis. They are required for DNA replication because the enzymes that catalyze this process, DNA polymerases, can only add new nucleotides to an existing strand of DNA...
for the leading strand synthesis. Both positive and negative sense strands of DNA are made. Double stranded intermediates are formed throughout the replication; this means the two strands, positive and negative sense, will be matched up..
Host Range
These viruses are capable of replication within all of the vertebrates. They are only limited by the virus they must infect with, also known as the helper virus. These helper viruses are necessary for the replication of the Dependovirus. A common helper virus in humans is the adenovirus. There is no known disease in humans associated with Dependovirus.Gene Therapy
The Dependovirus is not a large enough virus to trigger an immune response; this makes it a good virus to use as a gene therapy tool. Gene therapyGene therapy
Gene therapy is the insertion, alteration, or removal of genes within an individual's cells and biological tissues to treat disease. It is a technique for correcting defective genes that are responsible for disease development...
is a possible treatment for a variety of disorders and diseases that are genetic in origin. Viral vectors are currently being developed to transport genes into human cells. Since this virus does not stimulate an immune response it can be used multiple times effectively without being neutralized before infection. Another reason these viruses are reliable vectors is the known insertion point for the genome. This virus always inserts its contents into the same place on chromosome 19. This predictability can cut down on the chances of inserting into an important area that might disrupt normal gene function or increase the risk of developing cancer.
At this time, one challenge using this virus as a therapy tool is the fact that the genome is fairly small. With less than 5kb in the genome the amount of genetic material that can fit into the capsid is limited. Work is currently being done to increase the amount of information this vector can deliver. This may be accomplished by the LTRs found at both the 5’ and 3’ end of the genome. Since the LTRs have the same sequence they will leave complementary strands exposed if they are removed. The complementary strands can undergo recombination
Genetic recombination
Genetic recombination is a process by which a molecule of nucleic acid is broken and then joined to a different one. Recombination can occur between similar molecules of DNA, as in homologous recombination, or dissimilar molecules, as in non-homologous end joining. Recombination is a common method...
and join two 5kb inserted fragments together.