Brief Histories of Retroviral Integration Research and Associated International Conferences

Abstract

The field of retroviral integration research has a long history that started with the provirus hypothesis and subsequent discoveries of the retroviral reverse transcriptase and integrase enzymes. Because both enzymes are essential for retroviral replication, they became valued targets in the effort to discover effective compounds to inhibit HIV-1 replication. In 2007, the first integrase strand transfer inhibitor was licensed for clinical use, and subsequently approved second-generation integrase inhibitors are now commonly co-formulated with reverse transcriptase inhibitors to treat people living with HIV. International meetings specifically focused on integrase and retroviral integration research first convened in 1995, and this paper is part of the Viruses Special Issue on the 7th International Conference on Retroviral Integration, which was held in Boulder Colorado in the summer of 2023. Herein, we overview key historical developments in the field, especially as they pertain to the development of the strand transfer inhibitor drug class. Starting from the mid-1990s, research advancements are presented through the lens of the international conferences. Our overview highlights the impact that regularly scheduled, subject-specific international meetings can have on community-building and, as a result, on field-specific collaborations and scientific advancements.

HPV, HBV, and HIV-1 Viral Integration Site Mapping: A Streamlined Workflow from NGS to Genomic Insights of Carcinogenesis

“…The modes of viral–host integration differ, respectively, among HPV, HBV, and HIV-1 to include faulty viral partitioning to daughter cells during mitosis, non-homologous end-joining (NHEJ). or micro-homology mediated end-joining (MMEJ) at double-strand DNA breaks, and provirus insertion [ 13 , 14 , 15 , 16 , 17 , 18 , 19 ]. cccDNA, covalently closed circular DNA; CCRS, chemokine receptor type 5; CXCR4, chemokine receptor type 4; DDR, DNA damage repair; dslDNA, double-stranded linear DNA; ECM, extracellular matrix; GFR, growth factor receptor; HSPG, heparin sulfate proteoglycan; NTCP, Na+-taurocholate co-transporting polypeptide; and rcDNA, relaxed circular DNA (figure created with ).…”

“…The integrated viral DNA leads to viral persistence, pathogenesis, and carcinogenesis [ 17 , 18 ]. For HIV-1, upon entering the immune cell, the RNA genome of the virion undergoes reverse transcription, resulting in a dsDNA (provirus) [ 19 ]. The provirus then enters the nucleus for insertion into the host genome at random sites by the HIV-1 integrase enzyme [ 19 ].…”