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Abstract Increasing efforts have been made to elucidate how genetic and environmental factors interact in Parkinson’s disease (PD). In the present study, we assessed the development of symptoms on a genetic PD rat model that overexpresses human α-synuclein (Snca +/+) at a presymptomatic age, exposed to a pro-inflammatory insult by intraperitoneal injection of lipopolysaccharide (LPS), using immunohistology, high-dimensional flow cytometry, constant potential amperometry, and behavioral analyses. A single injection of LPS into WT and Snca +/+ rats triggered long-lasting increase in the activation of pro-inflammatory microglial markers, monocytes, and T lymphocytes. However, only LPS Snca +/+ rats showed dopaminergic neuronal loss in the substantia nigra pars compacta (SNpc), associated with a reduction in the release of evoked dopamine in the striatum. No significant changes were observed in the behavioral domain. We propose our double-hit animal as a reliable model to investigate the mechanisms whereby α-synuclein and inflammation interact to promote neurodegeneration in PD.

OBJECTIVES/GOALS: The major obstacle to an effective cure or remission for HIV infection is the integration of HIV into the genome of long-lived resting cells which constitute the so-called viral reservoir. With this study we want to elucidate the changes of the gut-associated HIV reservoir at different stages of viral suppression METHODS/STUDY POPULATION: Recent studies have shown that after long-term (>7 years) clinical suppression of peripheral HIV RNA, the circulating viral reservoir does not seem to decline further and, in fact may expand. The gastrointestinal associated lymphoid tissue (GALT) harbors by far the largest fraction of the latently infected cells, however not much is known about its changes over time.We thus quantified the HIV viral reservoir in the GALT by identifying HIV viral transcripts via 10X single-cell RNA sequencing at two GALT-sites in five PWH and compared the amount of HIV RNA found in the group of PWH with early (< 7years) vs late (> 7years) peripheral virological suppression (plasma HIV RNA 7yrs, 0 (0-4) HIV transcripts were identified in the ileum and 7 (14-11) in the colon. Based on these preliminary results we plan to expand our cohort and confirm these results using Proviral DNA quantification. We anticipate that the viral decay in the GALT will follow a slower dynamic than what has been reported for the peripheral blood achieving a steady state after more than 7 years of peripheral viral suppression. DISCUSSION/SIGNIFICANCE: Despite the remarkable progress the survival and quality of life of PWH, after forty years from its first discovery, HIV infection remains uncurable. Considering its critical role, efforts are needed to better understand the dynamics of the GALT-associated HIV reservoir.

Abstract Gastrointestinal symptoms are common in COVID-19 patients but the nature of the gut immune response to SARS-CoV-2 remains poorly characterized, partly due to the difficulty of obtaining biopsy specimens from infected individuals. In lieu of tissue samples, we measured cytokines, inflammatory markers, viral RNA, microbiome composition, and antibody responses in stool samples from a cohort of 44 hospitalized COVID-19 patients. SARS-CoV-2 RNA was detected in stool of 41% of patients and more frequently in patients with diarrhea. Patients who survived had lower fecal viral RNA than those who died. Strains isolated from stool and nasopharynx of an individual were the same. Compared to uninfected controls, COVID-19 patients had higher fecal levels of IL-8 and lower levels of fecal IL-10. Stool IL-23 was higher in patients with more severe COVID-19 disease, and we found evidence of intestinal virus-specific IgA responses associated with more severe disease. We provide evidence for an ongoing humeral immune response to SARS-CoV-2 in the gastrointestinal tract, but little evidence of overt inflammation.