ARTICLE: Dynamics of natural and pharmacologic control of an SIV variant with an envelope trafficking defect
AUTHORS: Kyle Rhodehouse, Carolin Zitzmann, Meghana Ravi, Ciara Armstrong, Milica Moskovljevic, Hannah P Moore, Courtney Schill, Emily J Fray, Mithra R Kumar, Toni Penney, Clara Krzykwa, Miranda R Stauss, Roger W Wiseman, David H O'Connor, Christine M Fennessey, Brandon F Keele, Jeffrey D Lifson, Ruy M Ribeiro, Alan S Perelson, James A Hoxie, Nicholas J Maness, Janet D Siliciano, Robert F Siliciano
JOURNAL: J Exp Med. 2026 Feb 2;223(2):e20251172. doi: 10.1084/jem.20251172. Epub 2025 Dec 5.
Abstract
Insights into HIV-1 pathogenesis have come from studies of viral dynamics. However, there is little information on viral dynamics in lentiviral infections in which viral replication is naturally controlled in a subset of infected individuals. We evaluated the decay of simian immunodeficiency virus (SIV) RNA and cell-associated SIV genomes in a nonhuman primate (NHP) model in which replication of an engineered SIV variant is naturally controlled by cellular immune responses in most infected animals. This variant lacks a trafficking motif in the gp41 cytoplasmic tail. A trajectory of control was evident by 21 days after infection. In animals with natural control, we observed similar biphasic decay of intact proviruses in blood and lymph nodes, at rates close to those in animals that failed to control the virus and were put on antiretroviral therapy (ART). Both natural control and ART effectively blocked viral evolution, but not persistence. Thus, in this NHP model, natural control can be nearly as effective as ART in controlling viral replication.
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