title: Impact of HIV-1 infection pathways on susceptibility to antiviral drugs and on virus spread.
abstract: The infection routes of HIV-1 can affect several viral properties, including dissemination, pathogenesis, and immune evasion. In this study, we evaluated the inhibitory activity of a wide variety of anti-HIV drugs, focusing on the impact that different infection pathways have on their efficacy. Compared to cell-free infection, inhibitory activities were reduced in cell-to-cell productive transmission for all drugs tested. We detected weak reporter-expressing target cells after cell-to-cell transmission in the presence of integrase strand transfer inhibitors (INSTIs). Further analysis revealed that this expression was mainly due to unintegrated circular HIV (cHIV) DNAs, consisting of 1-LTR and 2-LTR circles. When in vitro-constructed cHIV DNAs were introduced into cells, the production of infectious and intercellular transmittable virions was observed, suggesting that cHIV DNA could be a source of infectious virus. These results highlight some advantages of the cell-to-cell infection mode for viral expansion, particularly in the presence of anti-retroviral drugs.
authors.affiliation: Institute for Virus Research, Kyoto University, Kyoto, Japan. Electronic address: kshimura@virus.kyoto-u.ac.jp.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Shimura
authors.affiliation: Institute for Virus Research, Kyoto University, Kyoto, Japan.
authors.forename: Paola
authors.initials: P
authors.lastname: Miyazato
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Oishi
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Fujii
authors.affiliation: Institute for Virus Research, Kyoto University, Kyoto, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Matsuoka
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology*; D002460:Cell Line; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D053586:Virus Internalization / Q000187:drug effects*; D057074:Virus Release / Q000187:drug effects*; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D019380:Anti-HIV Agents
keywords: Anti-HIV drug; Cell-free; Cell-to-cell; Circular HIV-1 DNA; HIV-1; Integration