What is the Difference Between Adenovirus and Adeno-Associated Virus

The main difference between adenovirus and adeno-associated virus is that adenovirus uses the host’s DNA replication machinery, whereas adeno-associated virus requires a helper adenovirus for replication.

Adenovirus and adeno-associated virus are two DNA viruses. They are non-enveloped viruses that are pathogenic. 

Key Areas Covered

1. What is Adenovirus
     – Definition, Facts, Importance
2. What is an Adeno-Associated Virus
     – Definition, Facts, Importance
3. Similarities Between Adenovirus and Adeno-Associated Virus
     – Outline of Common Features
4. Difference Between Adenovirus and Adeno-Associated Virus
     – Comparison of Key Differences

Key Terms 

Adeno-Associated Virus, Adenovirus

What is Adenovirus

Adenovirus is a medium-sized DNA virus with an icosahedral protein capsid. Its genome contains double-stranded DNA. However, it does not have an envelope. The size of the adenovirus is 90-100 nm. Its icosahedral capsid contains 240 hexon proteins. The genome of the adenovirus is linear and non-segmented. The size of the genome is 26 to 48 kb. Moreover, it is a pathogenic virus with many hosts, including vertebrates. It causes a wide range of illnesses, including mild respiratory infections in children and life-threatening, multi-organ diseases in people with a weakened immune system. There are more than 50 serotypes of adenoviruses causing various illnesses.

Figure 1: Adenovirus

Furthermore, the genome of adenovirus contains 22-40 genes. Generally, its viral particles enter the host cell through endosomes. Adenovirus also has a high efficiency of infection. However, its DNA does not integrate into the genome of the host. 

What is an Adeno-associated Virus

Adeno-associated virus is a small virus that infects humans and other primates. The diameter of the virus is 26 nm. Furthermore, it is a replication-defective, non-enveloped virus. The size of the adeno-associated virus’s genome is 4.8 kb. It is an attractive candidate for viral vectors in gene therapy. This virus infects both dividing and quiescent cells and exists at the extrachromosomal level without integrating into the host’s genome. However, the genes carried by the virus integrate into the host genome.

Figure 2: Adeno-Associated Virus 

Moreover, the lack of pathogenicity is a notable feature of adeno-associated viruses in gene therapy. It infects non-dividing cells. Additionally, the virus can integrate its genome into the human host genome at the specific site in the human chromosome 19. Random integrations can occur with a negligible frequency. In gene therapy, the gene of interest can be inserted between inverted terminal repeats (ITRs). 

Similarities Between Adenovirus and Adeno-Associated Virus

• Adenovirus and adeno-associated virus are two DNA viruses.
• They are pathogenic viruses that infect vertebrates.
• They are enveloped viruses containing icosahedral capsids.
• Both are used as recombinant delivery systems.
• They are non-integrating viruses. 

Difference Between Adenovirus and Adeno-Associated Virus

Definition

Adenovirus refers to a member of a family of viruses that can cause respiratory, eye, and gastrointestinal infections. In contrast, adeno-associated virus refers to small viruses infecting humans and other primate species. 

Genome

Adenovirus is a double-stranded DNA virus, while adeno-associated virus is a single-stranded DNA virus.  

Size 

The size of the adenovirus is 90-100 nm, while the size of the adeno-associated virus is 25 nm.

Replication

Adenovirus uses the host’s DNA replication machinery, while adeno-associated virus requires a helper adenovirus for replication.

Packaging Capacity

The packaging capacity of adenovirus is 8-36 kb, while the packaging capacity of adeno-associated virus is 4.7 kb.

Transduction Efficiency

The transduction efficiency of adenovirus is high, while the transduction efficiency of adeno-associated virus is moderate.

Expression

The expression of adenovirus is transient, while the expression of the adeno-associated virus is transient or stable. 

Immunogenicity 

The immunogenicity of adenovirus is high, while the immunogenicity of adeno-associated virus is low.

Conclusion

In brief, adenovirus and adeno-associated viruses are two non-enveloped DNA viruses. Adenovirus contains a ds DNA genome. The size of adenovirus is 90-100 nm. Adenovirus uses the host’s DNA replication machinery for DNA replication. The packaging capacity of adenovirus is 8-36 kb, and the transduction efficiency of adenovirus is high. The expression of the adenovirus is transient. The immunogenicity of adenovirus is high. At the same time, the adeno-associated virus is 25 nm long and contains a ssDNA genome. Notably, the adeno-associated virus requires a helper adenovirus for replication. The packaging capacity of the adeno-associated virus is 4.7 kb. Transduction efficiency is moderate in adeno-associated viruses. Its expression can be transient or stable. The immunogenicity of the adeno-associated virus is low. Therefore, the main difference between an adenovirus and an adeno-associated virus is the type of replication. 

References:

1. Doerfler W. Adenoviruses. In: Baron S, editor. Medical Microbiology. 4th edition. Galveston (TX): University of Texas Medical Branch at Galveston; 1996. Chapter 67.
2. Naso MF, Tomkowicz B, Perry WL 3rd, Strohl WR. Adeno-Associated Virus (AAV) as a Vector for Gene Therapy. BioDrugs. 2017 Aug;31(4):317-334. doi: 10.1007/s40259-017-0234-5. PMID: 28669112; PMCID: PMC5548848.

Image Courtesy:

1. “Adv-D26 7-24-2021 1 ps” By Dr. Victor Padilla-Sanchez, PhD– Own work (CC-BY SA 4.0) via Commons Wikimedia
2. “Adeno-associated virus serotype AAV2” By Jazzlw.- Own Work (CC-BY SA 4.0) via Commons Wikimedia