HIV-1 infection remains a public health problem with no cure. Although antiretroviral therapy (ART) is effective for suppressing HIV-1 replication, it requires lifelong drug administration due to a stable reservoir of latent proviruses and may cause serious side effects and drive the emergence of drug-resistant HIV-1 variants. Gene therapy and cell therapy offer alternative approaches to ART, such as introducing therapeutic nucleic acids into target cells or generating a population of CD4+ T cells with a dysfunctional CCR5. To date, six cases of AIDS cure have provided proof of concept that HIV-1 can be cured. However, such an approach through stem cell transplantation is not feasible on a large scale to cure HIV-1 infection.

The research group led by Prof. Qinxue HU at the Wuhan Institute of Virology of the Chinese Academy of Sciences developed a therapeutic strategy for eliminating HIV-1 positive cells. Their findings, entitled "Tat-dependent Conditionally Replicating Adenoviruses Expressing Diphtheria Toxin A for Specifically Killing HIV-1 Infected Cells”, have been published in Molecular Therapy.

Based on the group's previous work on adenovirus immunogenicity and gene transduction (Vaccine. 2018, 36(29):4287-4297; J Gen Virol. 2015, 96(8):2381-2393), they constructed and investigated the antiviral effects of an HIV-1 Tat-dependent conditionally replicating adenovirus (Tat-CRAds-DTA), and then evaluated its anti-HIV-1 efficacy both in vitro and in vivo. Tat-CRAds-DTA exhibited no significant cytotoxicity to HIV-1 negative cells. It selectively proliferated and expressed the diphtheria toxin A chain (DTA) only in HIV-1 infected cells. DTA specifically induced death in HIV-1 infected cells and suppressed HIV-1 replication. Furthermore, in the humanized mouse model infected with HIV-1, Tat-CRAds-DTA demonstrated significant therapeutic efficacy. Their findings validate the potential of Tat-CRAds-DTA as a novel therapy for treating HIV-1 infection.

PhD student Fengfeng NI at the Wuhan Institute of Virology is the first author of the paper in Molecular Therapy, with Prof. Qinxue HU and Dr. Yalan LIU serving as the corresponding authors. Their study was supported by the National Key Research and Development Program, China, and the National Natural Science Foundation of China.

Paper links:

https://doi.org/10.1016/j.ymthe.2024.05.015

https://www.cell.com/molecular-therapy-family/molecular-therapy/abstract/S1525-0016(24)00317-4?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1525001624003174%3Fshowall%3Dtrue