Manabe, Y. C. | bioRxiv Science

bioRxiv2022

Within-host evolutionary dynamics and tissue compartmentalization during acute SARS-CoV-2 infection

The global evolution of SARS-CoV-2 depends in part upon the evolutionary dynamics within individual hosts with varying immune histories. To characterize the within-host evolution of acute SARS-CoV-2 infection, we deep sequenced saliva and nasal samples collected daily from immune and unvaccinated individuals early during infection. We show that longitudinal sampling facilitates high-confidence genetic variant detection and reveals evolutionary dynamics missed by less-frequent sampling strategies. Within-host dynamics in both naive and immune individuals appeared largely stochastic; however, we identified clear mutational hotspots within the viral genome, consistent with selection and differing between naive and immune individuals. In rare cases, minor genetic variants emerged to frequencies sufficient for forward transmission. Finally, we detected significant genetic compartmentalization of virus between saliva and nasal swab sample sites in many individuals. Altogether, these data provide a high-resolution profile of within-host SARS-CoV-2 evolutionary dynamics.

microbiology↗

bioRxiv2019

B cell Compartmentalisation in Blood and Cerebrospinal Fluid of HIV- Infected Ugandans with Cryptococcal Meningitis

BackgroundActivated B cells modulate infection by differentiating into pathogen-specific antibody-producing effector plasmablasts/plasma cells, memory cells and immune regulatory B cells. In this context, the B cell phenotypes that infiltrate the central nervous system during HIV and cryptococcal meningitis co-infection are ill defined.\n\nMethodsWe characterized clinical parameters, mortality and B cell phenotypes in blood and CSF by flow cytometry in HIV-infected adults with cryptococcal (n=31), and non-cryptococcal meningitis (n=12), and heathy control subjects with neither infection (n=10).\n\nResultsActivation of circulating B cells (CD21low) was significantly higher in blood of subjects with HIV infection compared with healthy controls, and greater yet in matched CSF B cells (p<0.001). Among B cell subsets, elevated frequencies of memory and plasmablasts/plasma cells most clearly distinguished the CSF from blood compartments. With cryptococcal meningitis, lower frequencies of expression of the regulatory protein PD-1 on plasmablasts/plasma cells in blood (median 7%) at presentation was associated with significantly decreased 28-day survival (29% (4/14 subjects)), whereas higher PD-1 expression (median 46%) characterized subjects with higher survival (88% (14/16 subjects)).\n\nConclusionWith HIV infection, B cell differentiation and regulatory markers are discrete elements of the circulating and CSF compartments with clinical implications for cryptococcal disease outcome, potentially due to their effects on the fungus and other local immune cells.

immunology↗