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: Kazuya Shimura, Paola Miyazato, Shinya Oishi, Nobutaka Fujii, Masao Matsuoka
• Journal: Virology (Virology) Vol. 484 Pg. 364-376 (Oct 2015) ISSN: 1096-0341 [Electronic] United States
• PMID: 26186575 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Anti-HIV Agents

Topics

• Anti-HIV Agents (pharmacology)
• Cell Line
• HIV-1 (drug effects, physiology)
• Humans
• Virus Internalization (drug effects)
• Virus Release (drug effects)
• Virus Replication (drug effects)