A helper dependent virus, also termed a gutless virus, is a synthetic

viral vector Viral vectors are tools commonly used by molecular biologists to deliver genetic material into cells. This process can be performed inside a living organism (''in vivo'') or in cell culture (''in vitro''). Viruses have evolved specialized molecul ...

dependent on the assistance of a

helper virus A helper virus is a virus that allows an otherwise-deficient coinfecting virus to replicate. These can be naturally occurring as with Hepatitis D virus, which requires Hepatitis B virus to coinfect cells in order to replicate. Helper viruses are a ...

in order to replicate, and can be used for purposes such as

gene therapy Gene therapy is a medical field which focuses on the genetic modification of cells to produce a therapeutic effect or the treatment of disease by repairing or reconstructing defective genetic material. The first attempt at modifying human DN ...

. Naturally-occurring

satellite viruses A satellite is a subviral agent that depends on the coinfection of a host cell with a helper virus for its replication. Satellites can be divided into two major classes: satellite viruses and satellite nucleic acids. Satellite viruses, which ar ...

are also helper virus dependent, and can sometimes be modified to become viral vectors.

Viral vector

Since the genome of the gutless virus does not include genes encoding the enzymes and/or structural proteins required to replicate, it is deemed safe for use in

since an infection cannot occur except in the presence of a suitable helper virus. Well established protocols allow scientists to propagate helper dependent viruses in the lab. However, using an actual helper virus poses problems when it comes to purification of a desired

transgenic A transgene is a gene that has been transferred naturally, or by any of a number of genetic engineering techniques, from one organism to another. The introduction of a transgene, in a process known as transgenesis, has the potential to change the ...

virus. Therefore, lab methods often utilize minimal fragments of the helper DNA that can serve this purpose without creating unwanted virus. This process usually involves the introduction of three separate DNA

plasmid A plasmid is a small, extrachromosomal DNA molecule within a cell that is physically separated from chromosomal DNA and can replicate independently. They are most commonly found as small circular, double-stranded DNA molecules in bacteria; how ...

s into a

eukaryotic Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...

cell line through a process called

transfection Transfection is the process of deliberately introducing naked or purified nucleic acids into eukaryotic cells. It may also refer to other methods and cell types, although other terms are often preferred: "transformation" is typically used to desc ...

. These plasmids contain either transgenic DNA or replication and

capsid A capsid is the protein shell of a virus, enclosing its genetic material. It consists of several oligomeric (repeating) structural subunits made of protein called protomers. The observable 3-dimensional morphological subunits, which may or may ...

encoding DNA, plus helper DNA. Every cell that is successfully transfected with all three DNA fragments will produce the necessary proteins to produce infective viruses. These viruses will only have transgenic DNA encapsidated and therefore once they've infected a patient's cell, they will not be capable of reproducing.

Satellite virus

Helper dependent viruses can also occur in nature without being "gutted". The term

satellite virus A satellite is a subviral agent that depends on the coinfection of a host cell with a helper virus for its replication. Satellites can be divided into two major classes: satellite viruses and satellite nucleic acids. Satellite viruses, which ar ...

has been given to a large group of viruses that all require the presence of another virus to replicate. Many of these are plant viruses, but animal viruses can be seen in the case of dependoviruses. Within the family

parvoviridae Parvoviruses are a family of animal viruses that constitute the family ''Parvoviridae''. They have linear, single-stranded DNA (ssDNA) genomes that typically contain two genes encoding for a replication initiator protein, called NS1, and the pr ...

, the dependovirus genus was given a distinct classification due to their dependence on another virus. The most widely known dependovirus is

adeno-associated virus Adeno-associated viruses (AAV) are small viruses that infect humans and some other primate species. They belong to the genus ''Dependoparvovirus'', which in turn belongs to the family ''Parvoviridae''. They are small (approximately 26 nm in di ...

(AAV) which was originally discovered as a contaminant in a sample of

simian The simians, anthropoids, or higher primates are an infraorder (Simiiformes ) of primates containing all animals traditionally called monkeys and apes. More precisely, they consist of the parvorders New World monkeys (Platyrrhini) and Catarrhi ...

adenovirus 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 the ...

. Though AAV is considered to be dependent on adenovirus, it is able to replicate in the presence of

herpesvirus ''Herpesviridae'' is a large family of DNA viruses that cause infections and certain diseases in animals, including humans. The members of this family are also known as herpesviruses. The family name is derived from the Greek word ''ἕρπειν ...

as well as certain cytotoxic events such as UV irradiation or some

carcinogen A carcinogen is any substance, radionuclide, or radiation that promotes carcinogenesis (the formation of cancer). This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes. Several radioactive substan ...

s During the course of a natural dependovirus infection, if the helper virus is not present, the dependovirus is often capable of integrating into the host genome and going into a

latent Latency or latent may refer to: Science and technology * Latent heat, energy released or absorbed, by a body or a thermodynamic system, during a constant-temperature process * Latent variable, a variable that is not directly observed but inferred ...

phase of its life cycle—effectively waiting for the next helper virus infection. For gene therapy uses, the vector is stripped of its ability to integrate. Because AAV can deliver transgenic material in a non-replicating form, it is a strong candidate for gene therapy and is currently used in about 8% of clinical trials. Hepatitis D virus (HDV) is an example of a replication defective, helper dependent ssRNA virus because it requires Hepatitis B virus (HBV) to provide HBV surface antigen (HBsAg) for the

encapsidation {{Short pages monitor