Adeno-associated virus infection and its impact in human health: an overview

Abstract

Discovered as a contaminant of adenovirus stocks in the 1960s, adeno-associated virus (AAV) is a mono-stranded DNA virus that depends on helper factors to replicate. Even though AAV is endemic in the human population (35–80%), it is remarkable that many issues concerning the natural infection by this virus remain unanswered. In this study, we reflect on the main basic aspects of AAV biology and provide an overview of the studies exploring the impact of AAV infection on human health, focusing on three major research areas including, (i) cervical and (ii) liver cancer, and (iii) reproductive system disorders. Conflicting results have been obtained into the association of AAV infection with the occurrence of adverse reproductive outcomes, such as placental complications, spontaneous abortion, and fertility disorders, or with a protective role in HPV-related cervical carcinogenesis. Noteworthy, recent reports have identified AAV insertional mutagenesis as a novel risk factor for the development of hepatocellular carcinoma. This latest finding raises concern regarding the widespread usage of AAV vectors in liver-targeted gene therapy.

Applications of CRISPR/Cas9 gene-editing technology in cancer

“…Its name comes from the fact that it was initially found to be an adenovirus preparation contamination [10]. Unlike Adenovirus, AAV is regarded as a secure and effective gene therapy vector because it is not known to induce any human diseases [11]. As several AAV serotypes have been demonstrated to be suitable for CRISPR-editing in particular tissues, a vast number of them enable tissue-targeted gene delivery [5].…”

Coinfections in human papillomavirus associated cancers and prophylactic recommendations

“…However, the functional association of AAV infection has ambiguous outcomes when considered in placental complications, fertility disorders and cancer-associated disorders. 38 Intra-species viral coinfections also play a crucial role in cancer progression. Previous reports suggest that all HPVgenotypes are not specifically targeted by vaccination; with the exception of HPV45 and HPV58, all other HPV-genotypes were coinfected with HPV16 and 18.…”

Postpandemic rebound of adeno‐associated virus type 2 (AAV2) infections temporally associated with an outbreak of unexplained severe acute hepatitis in children in the United Kingdom

“…The stored data included age band, partial postcode, any recorded symptoms or clinical information, referral source, month of sample collection, and the results of other virological tests for each sample. For the samples from 2022, the majority were nose and throat swabs (117) with the remainder consisting of nasopharyngeal secretions (14), nose swabs (10), throat swabs (6), and bronchoalveolar lavage (BAL) (2). For the control cohort, the samples predominantly comprised nasopharyngeal aspirates or swabs (130/141) and were routinely screened for the following respiratory viruses by previously described polymerase chain reaction (PCR) assays 18,19 : AdV, influenza A and B viruses, parainfluenza virus type 1 (PIV-1), PIV-2, PIV-3, and respiratory syncytial virus (RSV).…”

“…AAVs are genetically diverse, with at least 13 serologically distinct types. 5,6 Human infection with AAV is common, with up to 80% of individuals having neutralizing antibodies to one or more serotype, the majority being directed against AAV2, although with considerable variation in prevalence depending on age, sex, and geographical region. 7 Infections are generally believed to be apathogenic, evoking only a minor inflammatory response, although they have been associated with mild hepatitis when used in gene therapy.…”

“…AAVs are genetically diverse, with at least 13 serologically distinct types 5,6 . Human infection with AAV is common, with up to 80% of individuals having neutralizing antibodies to one or more serotype, the majority being directed against AAV2, although with considerable variation in prevalence depending on age, sex, and geographical region 7 …”