Transcriptional transactivation turns human iPSC-derived macrophages into an adenovirus-producing cell state
Summary
AdV are widespread, cause severe respiratory disease, persist in immune cells, and, upon reactivation, cause life-threatening conditions in immunocompromised individuals. Here, we show that human macrophages are either protected or susceptible to AdV, depending on the cell state, notably in an interferon-independent manner. The decisive cell state switch is the viral immediate-early transcription modulator E1A, which turns a repressive state into a permissive one and allows for the transactivation of dormant AdV-C5 genomes and viral progeny production. The data raise the possibility that macrophages are a hub for AdV persistence and epigenetic reactivation in vivo, in line with the notion that these cells resist immune clearance and serve as reservoirs for HIV, herpesvirus, SARS-CoV-2, or rubella virus infections.
| Authors | Suomalainen M, Haenseler W, Kolibius J, Plückthun A, Hearing P, Greber UF |
|---|---|
| Journal | Journal of virology |
| Publication Date | 2026 May 4;100(6):e0039226 |
| PubMed | 42080870 |
| PubMed Central | PMC13288996 |
| DOI | 10.1128/jvi.00392-26 |