Clades of Adeno-Associated Viruses Are Widely Disseminated in Human Tissues

TLDR

Adeno‑associated virus (AAV) is a promising vector for human gene therapy, yet infections are common in humans and understudied due to limited viral sequence analyses. The study employed molecular techniques to detect endogenous AAV sequences in 18 % of screened human tissues, predominantly in liver and bone marrow. Endogenous AAV was identified in 18 % of tissues, revealing diverse clades—including a hybrid of two serotypes and a cross‑species clade shared with nonhuman primates—underscoring their biological relevance and implications for gene‑therapy vector design.

Abstract

ABSTRACT The potential for using Adeno-associated virus (AAV) as a vector for human gene therapy has stimulated interest in the Dependovirus genus. Serologic data suggest that AAV infections are prevalent in humans, although analyses of viruses and viral sequences from clinical samples are extremely limited. Molecular techniques were used in this study to successfully detect endogenous AAV sequences in 18% of all human tissues screened, with the liver and bone marrow being the most predominant sites. Sequence characterization of rescued AAV DNAs indicated a diverse array of molecular forms which segregate into clades whose members share functional and serologic similarities. One of the most predominant human clades is a hybrid of two previously described AAV serotypes, while another clade was found in humans and several species of nonhuman primates, suggesting a cross-species transmission of this virus. These data provide important information regarding the biology of parvoviruses in humans and their use as gene therapy vectors.