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Adeno-associated Virus

What It Is, Transmission, Signs, Symptoms, Diagnosis, and More

Author: Georgina Tiarks

Editors: Alyssa Haag, Emily Miao, PharmD, Kelsey LaFayette, DNP

Illustrator: Jessica Reynolds, MS

Modified: 13 May 2024

What is adeno-associated virus?

Adeno-associated viruses (AAV) are non-enveloped, single-stranded DNA viruses heavily studied for their use in gene therapy. The virus belongs to a subset of the Parvoviridae family and in the Dependoparvovirus genus, named because of how reliant they are on other viruses to replicate. AAV must be coinfected alongside helper viruses such as adenovirus, herpes virus simplex type 1 (HSV-1), human cytomegalovirus (CMV), varicella zoster virus (VZV), and human herpesvirus-6 (HHV-6) to replicate. There are 12 AAV serotypes, which can be manipulated for gene delivery. Each serotype has a different tropism, meaning they exhibit a preference for different cell types and tissues in the body (e.g., skeletal muscle, hepatocyte, lymphocytes). AAV is non-pathogenic, meaning it causes no known initial symptoms, and because it does not cause disease in humans, it has shown to be promising in gene therapy research. 

Adeno-associated virus was originally discovered as a contaminant to adenovirus cultures. It has a small amount of DNA contained inside a protective protein shell. Within the DNA, two AAV genes, rep and cap, provide blueprints for the production of structural and replication proteins. The three structural capsid proteins are VP1, VP2, and VP3, while the proteins required for replication are known as Rep40, Rep52, Rep68, and Rep78.

How can adeno-associated virus be used in gene therapy?

Further research has shown that the viral genome of AAV can be modified to transport modified DNA into target cells, making it a target for gene therapy research. In particular, it can transport DNA or RNA into cells that are missing a specific sequence. For example, in Duchenne muscular dystrophy, the mutations in the DMD gene cause a deficiency of the dystrophin protein. AAV can be used to transport an exogenous dystrophin into the cells of the body. This research is particularly useful for single-gene diseases that are missing a singular protein. Currently, AAV serotype 2 is also being studied for use in ovarian cancer treatments, hemophilia B, blindness, and spinal muscular atrophy.

How is adeno-associated virus transmitted?

The adeno-associated virus can be transmitted through various forms of contact with an infected host. The virus has been isolated from blood, cervical mucus, semen, hepatocytes, amniotic fluid, and epithelial cells. Any direct or indirect contact (e.g., touching infected surfaces) with infected fluid could cause transmission. It is uncertain whether vertical transmission from mother to baby can occur. Even without a helper virus, AAV can bind to a host cell receptor (e.g., heparan sulfate proteoglycan, sialic acid) and transfer its viral genome into the host cell through endocytosis.

What signs and symptoms does adeno-associated virus infection cause?

The adeno-associated virus infection does not cause any known acute signs or symptoms. However, individuals can remain infected for their lifetime. Between 30 to 85% of the population has antibodies to AAV. 

Recent research has found a correlation between those infected with AAV2 and childhood hepatitis. Studies have also found that AAV can be linked to reproductive system disorders, specifically an increased rate of miscarriage and liver cancer. Interestingly, those infected with AAV have also been found to have a lower likelihood of developing cervical carcinoma, indicating a protective effect. Although AAV gene therapy is promising, more research is needed to ensure there are no long-term adverse effects. 

How is an adeno-associated virus infection diagnosed and treated?

A polymerase chain reaction (PCR) test is required to detect the AAV viral genome, and because AAV presents initially as largely asymptomatic, there is no treatment for adeno-associated virus.

What are the most important facts to know about adeno-associated virus?

Adeno-associated virus (AAV) is a single-stranded DNA virus used in gene therapy research. It is non-pathogenic in humans and cannot replicate without the presence of other viruses. Therefore, it can be used in gene therapy to carry modified DNA into target cells. AAV can be transmitted through contact with infectious material such as feces, blood products, semen, cervical mucus, and amniotic fluid. Infection is asymptomatic. It can be diagnosed using a PCR test, and there is no treatment. 

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