Dependovirus

Dependovirus (synonym: Adeno-associated virus group) is a genus of the Parvoviridae viruses, 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 capsids in its host cell without the cell being coinfected by a helper virus such as an adenovirus, a herpesvirus, or a vaccinia virus.

Biology

This single stranded (ss) DNA virus has a genome size of 4.7 kb or 47,000 nucleotides. The genome consists of one long strand of DNA. 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 ^[1]. The genome has only two genes. One is the structural capsid protein, cap. The cap transcript can be spliced to form two RNAs, one for virion protein 1 (VP1) and the other goes on to eventually make VP2 and VP3. These virion proteins form the capsid, or protective protein coat. 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^[1]. The capsid is made of 60 kite-shaped wedge proteins called capsomers^[2]. These capsomers are VP1, VP2, and VP3. Each capsid is made from 5 VP1, 5 VP2, and 50 VP3 proteins. The capsid measures 22 nm^[1]. Like most viruses the Dependovirus has a highly geometric capsid shape. The 60 wedge shaped proteins make an icosahedral shape. The proteins that make the capsid stick out making the capsid appear like a ball with spikes and a number of depressions. The capsid does not have an envelope^[2].

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^[3].

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 therapy 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 ^[4]. 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 vecto 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^[5].

References

1. ^ ^{a b c} Gonçalves, M (2005). "Adeno-associated virus: from defective virus to effective vector". Virology journal 2 (1): 43–60. http://journals.ohiolink.edu/ejc/pdf.cgi/Gonalves_Manuel.pdf?issn=1743422x&issue=v02i0001&article=43_avfdvtev. 
2. ^ ^{a b} ICTVdB Management; Ed. Büchen- Osmond, C. (2006). "ICTVdB - The Universal Virus Database, version 4: Dependovirus". Columbia University, New York, USA. Archived from the original on 2006-04-25. http://www.ncbi.nlm.nih.gov/ICTVdb/ICTVdB/00.050.1.03.htm. Retrieved May 4, 2009. 
3. ^ Agbandje, M, Parrish, C. R., and Rossmann, M. G (1995). "The recognition of parvovirus capsids by Antibodies". Virology 6: 219–231. http://journals.ohiolink.edu/ejc/pdf.cgi/Agbandje_Mavis_.pdf?issn=10445773&issue=v06i0004&article=219_tropcba. 
4. ^ Excoffon, K, et al. (2009). "Directed evolution of adeno-associated virus to an infectious respiratory virus". Proceedings on the National Academy of Science 106 (10): 3865–3870. http://www.pnas.org/content/106/10/3865.full.pdf+html. 
5. ^ Ghosh, A., Yue, Y., Lai, Y., and Duan, D. (2008). "A Hybrid Vector System Expands Adeno-associated Viral Vector Packaging Capacity in a Transgene- Independent manner". Molecular Therapy 16 (1): 124–130. http://www.nature.com/mt/journal/v16/n1/pdf/6300322a.pdf. 

External links

• ViralZone: Dependovirus