Ahelper dependent virus, also termed agutless virus, is a syntheticviral vector dependent on the assistance of ahelper virus in order to replicate,[1] and can be used for purposes such asgene therapy. Naturally-occurringsatellite viruses are also helper virus dependent, and can sometimes be modified to become viral vectors.
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 ingene therapy since an infection cannot occur except in the presence of a suitable helper virus.[2]
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 desiredtransgenic 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 DNAplasmids into aeukaryotic cell line through a process calledtransfection. These plasmids contain either transgenic DNA orreplication andcapsid 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.[3]
Helper dependent viruses can also occur in nature without being "gutted". The termsatellite 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,[4] but animal viruses can be seen in the case ofdependoviruses.
Within the familyparvoviridae, the dependovirus genus was given a distinct classification due to their dependence on another virus. The most widely known dependovirus isadeno-associated virus (AAV) which was originally discovered as a contaminant in a sample ofsimianadenovirus.[5] Though AAV is considered to be dependent on adenovirus, it is able to replicate in the presence ofherpesvirus as well as certain cytotoxic events such asUV irradiation or somecarcinogens[6] During the course of a natural dependovirus infection, if the helper virus is not present, the dependovirus is often capable ofintegrating into the host genome and going into alatent phase of its life cycle—effectively waiting for the next helper virus infection.[6] 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.[7]
Hepatitis D virus (HDV) is an example of a replication defective, helper dependent ssRNA virus because it requiresHepatitis B virus (HBV) to provide HBV surface antigen (HBsAg) for theencapsidation of its genome. The envelope proteins on the outer surface of HDV are entirely provided by HBV.
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