Adeno-associated Virus · What It Is, Transmission, Signs, Symptoms, Diagnosis, and More

Adeno-associated virus (AAV) is a non-enveloped, single-stranded DNA virus heavily studied for its use in gene therapy. The virus belongs to the Dependoparvovirus genus, a subset of the Parvoviridae family, so named because it relies on other viruses for replication. In fact, AAV replication is dependent on coinfection with helper viruses such as adenovirus, herpes simplex virus type 1 (HSV-1), human cytomegalovirus (CMV), varicella zoster virus (VZV), and human herpesvirus-6 (HHV-6). In the absence of helper viruses, AAV integrates its genome into the host cell, and while most copies are eliminated rapidly, some can persist indefinitely. At least 13 AAV serotypes exist, each with a different tissue tropism - i.e., 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 does not cause disease in humans, making it a promising tool for gene therapy research.  

Adeno-associated virus was originally discovered as a contaminant of adenovirus cultures. It contains a small amount of DNA enclosed in a protective protein shell. Within the DNA, three AAV genes,  Rep (replication), Cap (capsid), and aap (assembly), provide blueprints for the production and building 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. 

AAV infection does not cause any signs or symptoms; however, the virus can persist within the host throughout their lifetime. Between 30 and 85% of the population has antibodies to AAV.  

 However, the effects of AAV infection on the human body are still under investigation. Recent research has found an association between AAV2 coinfection, the HLA-DRB1*04:01 allele (i.e.,  genetic variant linked to immune response) and acute hepatitis in children. Evidence also suggests a link between AAV and reproductive system disorders, specifically an increased rate of miscarriage, and liver cancer. Interestingly, AAV infection has been associated with a lower likelihood of developing cervical carcinoma, suggesting a protective effect.