Chaunzwa, M. | Search bioRxiv

bioRxiv2026

Distinct phases of immune system programming during ART-suppressed immunodeficiency virus infection

People living with HIV (PLWH) on suppressive antiretroviral therapy (ART) can face non-AIDS complications, partially driven by chronic immune activation. To define immune perturbations during ART-suppressed viral infection, we performed longitudinal single-cell transcriptomic and plasma proteomic analysis of rhesus macaques infected with SIVmac239M and ART-treated for 70 weeks. We identified broad, bi-phasic immune changes. Acute infection involves an interferon-driven signature, correlated with viral replication, that largely resolves with viral control. Cell-associated virus correlated with interferon-stimulated genes in most tissues; however, this was blunted in gut-associated lymph nodes, a feature that may contribute to reservoir persistence. Separate alterations manifest 54-66 weeks-post-infection, after 40 weeks of viral suppression, including broad TGF-{beta} and NF-kB signaling and discrete bursts of inflammatory monocytes, largely restricted to bone marrow. These data highlight the biphasic remodeling of long-term ART-suppressed HIV, identifying specific tissues and cell populations with dysregulation, with implications for the treatment of PLWH.

immunology↗

bioRxiv2026

TEDEdb: a large-scale resource and multi-cohort analysis of transposable element differential expression in cancer

The human genome consists of nearly 50% repetitive DNA, referred to for decades as "junk DNA". These repetitive sequences, usually under the strict control of epigenetic silencing, have been observed to be aberrantly expressed in cancer. Some of these expressed sequences, e.g., transposable elements (TEs), can induce innate immune responses when de-repressed following treatment with epigenetic therapies. As a result, epigenetic therapy has been suggested to augment cancer therapies. TEs are traditionally ignored in most RNA-seq studies and their expression is often excluded from publicly available data sources. Thus, the vast amount of publicly available RNA-seq data is an untapped resource for exploring the role of TE expression in cancer and cancer treatment. Here, we present a uniform re-analysis of over 7,000 RNA-seq samples, encompassing more than 2,000 differential expression experiments across 220 cancer cell lines and 700 drug treatments. We observed that TE expression is more prone to batch effects than gene expression alone, necessitating the use of meta-analysis techniques to probe the dataset for global trends. We confirm that DNMTi and HDACis are powerful inducers of TEs. We also show that non-epigenetic compounds such as CDK and topoisomerase inhibitors can also induce robust up-regulation of transposable elements and confirm that this TE induction is consistent with viral mimicry response. We make all of the reprocessed data, web application, and database publicly available at: https://dataexplorer.coriell.org/TEDEdb/

cancer biology↗