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

viral vector A viral vector is a modified virus designed to gene delivery, deliver genetic material into cell (biology), cells. This process can be performed inside an organism or in cell culture. Viral vectors have widespread applications in basic research, ...

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 Health technology, medical technology that aims to produce a therapeutic effect through the manipulation of gene expression or through altering the biological properties of living cells. The first attempt at modifying human DNA ...

. Naturally-occurring satellite viruses 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 and ...

s into a

eukaryotic The eukaryotes ( ) constitute the Domain (biology), domain of Eukaryota or Eukarya, organisms whose Cell (biology), cells have a membrane-bound cell nucleus, nucleus. All animals, plants, Fungus, fungi, seaweeds, and many unicellular organisms ...

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 des ...

. 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 m ...

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 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

dependovirus ''Dependoparvovirus'' (formerly ''Dependovirus'' or Adeno-associated virus group) is a genus in the subfamily ''Parvovirinae'' of the virus family (biology), family ''Parvoviridae''; they are Group II viruses according to the Baltimore classific ...

es. 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 (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 monkey, Platyrrhini (New World mon ...

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 t ...

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

herpesvirus ''Orthoherpesviridae'', previously named and more widely known as ''Herpesviridae'', is a large family of DNA viruses that cause infections and certain diseases in animals, including humans. The members of this family are commonly known as herp ...

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

carcinogen A carcinogen () is any agent that promotes the development of cancer. Carcinogens can include synthetic chemicals, naturally occurring substances, physical agents such as ionizing and non-ionizing radiation, and biologic agents such as viruse ...

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 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 of its genome. The envelope proteins on the outer surface of HDV are entirely provided by HBV.

References

{{Self-replicating organic structures, state=collapsed Virology