Detection of adeno-associated virus type 2 in human peripheral blood cells

The non-pathogenic human parvovirus, adeno-associated virus (AAV) is helper virus-dependent. However, it integrates into the cellular genome in the absence of its helper viruses. Therefore it could become a useful vector for gene therapy. Previous studies and our own results have shown that 40 to 80% of adults are seropositive for AAV and that seroconversion occurs during the first few years of life, but little is known about the route of natural infection with the virus. We used the polymerase chain reaction to detect the AAV-2 genome and identify AAV sequences within peripheral blood leukocytes (PBLs). We could detect AAV in PBLs of two of 55 healthy blood donors, and two of 16 haemophilic patients. AAV DNA replication and viral protein production in PBLs propagated in tissue culture were also examined. AAV DNA replicated very efficiently in the presence of helper adenovirus, but capsid proteins were produced at a lower level and the yield of infectious virus was very low. Our findings prove that in vivo infection of PBLs occurs, and that PBLs could mediate the spread of AAV infection to different body tissues.