Biology subjects

Rodriguez, A. E.

Publications and source records attributed to Rodriguez, A. E..

3 recordsLinked to original sources

bioRxiv2026

Multiomic and Spatial Profiling of Colorectal Tissue Reveals Viral Persistence and Immune Dysregulation in Long COVID

Long COVID (LC) - a chronic condition characterized by persistent, debilitating symptoms following SARS-CoV-2 infection - has emerged as a major public health challenge. Although many interrelated mechanisms have been proposed as drivers of LC, the root causes have yet to be identified, posing significant challenges for therapeutic development. While many blood-based studies have been conducted, they have not yielded conclusive mechanistic insights into LC pathogenesis. Attention has therefore turned toward direct tissue investigation, with the gastrointestinal (GI) tract becoming a major focus due to evidence that virus or viral components can persist at this site for months to years following an episode of COVID-19. Here, we performed a high-dimensional characterization of colorectal tissue and peripheral blood in a highly characterized cohort of 44 people with LC and 13 recovered controls. We profiled SARS-CoV-2 persistence, host immune responses, and tissue inflammation using bulk and single-cell RNA sequencing, nCounter RNA probe hybridization, quantitative PCR, metagenomic next-generation sequencing, plasma proteomics, high-dimensional spectral flow cytometry, in situ-hybridization/immunohistochemistry, and single-cell digital spatial omics. Our results support a model in which LC is driven by long-term immune dysregulation and perturbations of the regulatory gut immune environment which imply ongoing viral persistence, although direct viral detection was only observed in a subset of participants. Specifically, we identify a tissue-based transcriptional environment in which SARS-CoV-2 activates innate myeloid immune signaling, driving chronic inflammation while simultaneously downregulating pathways responsible for immune-mediated clearance of infected cells, including antigen presentation, phagocytosis, cytotoxic immune cell trafficking, and granzyme production. Importantly, signatures in peripheral blood are considerably weaker than those observed in tissue. Together, these findings provide a direct biological rationale for therapeutic strategies in LC aimed at enhancing or redirecting cytotoxic immune function to overcome immune dysregulation and clear persistent viral reservoirs.

immunology↗

bioRxiv2026

Early immune responses anticipate HIV rebound and precede viral control

Sustained viral suppression following antiretroviral treatment (ART) cessation is a major goal of HIV cure research1. Rare individuals mount immune responses able to control viral rebound without intervention2,3, however, the earliest moments in which these responses form remain poorly defined. We performed an intensively sampled, prospective analytical treatment interruption (ATI) to study the initial immune response to rebound and to understand its role in defining subsequent virus control. Profiling of peripheral blood mononuclear cells and plasma revealed consistent immune activation prior to systemic rebound, including upregulation of antiviral transcriptional pathways, expansion of CD16++ non-classical monocytes, and increases of inflammatory and antiviral soluble plasma proteins. Individuals with prior viral control (controllers) diverged from non-controllers with a slower slope of rebound, a longer period of immune activity prior to rebound, and engagement of a multifaceted immune program with less systemic inflammation. An intermediate immune signature emerged in a separate ATI cohort of individuals who experienced delayed rebound after receiving broadly neutralizing antibodies4, suggesting that immunotherapy can induce a potentially protective pre-rebound immune response. Together, these data resolve the earliest systemic host immune responses to HIV rebound and demonstrate broad immune differences associated with HIV control phenotypes.

immunology↗

bioRxiv2018

Directed evolution of Escherichia coli with lower-than-natural plasmid mutation rates

Unwanted evolution of designed DNA sequences limits metabolic and genome engineering efforts. Engineered functions that are burdensome to host cells and slow their replication are rapidly inactivated by mutations, and unplanned mutations with unpredictable effects often accumulate alongside designed changes in large-scale genome editing projects. We developed a directed evolution strategy, Periodic Reselection for Evolutionarily Reliable Variants (PResERV), to discover mutations that prolong the function of a burdensome DNA sequence in an engineered organism. Here, we used PResERV to isolate E. coli cells that replicate ColE1 plasmids with higher fidelity. We found mutations in DNA polymerases I and IV and in RNase E that reduce plasmid mutation rates by 6-to 30-fold. The PResERV method implicitly selects to maintain the growth rate of host cells, and high plasmid copy numbers and gene expression levels are maintained in some of the evolved E. coli strains, indicating that it is possible to improve the genetic stability of cellular chassis without encountering trade-offs in other desirable performance characteristics. Utilizing these new antimutator E. coli and applying PResERV to other organisms in the future promises to prevent evolutionary failures and unpredictability to provide a more stable genetic foundation for synthetic biology.

evolutionary biology↗