Fig. 4: Off-ART, low-viraemic macaques demonstrate linkage between tissue outlier barcodes and rebounding virus in plasma.

a,b, Two low-viraemia macaques (LV1 (a) and LV2 (b)) each had evidence of two rebounding barcode lineages in plasma, but none were identified as outliers in any analysed necropsy tissue. Right panels show barcode proportional distribution in peak primary and rebound plasma. LV2 showed evidence of two outlier barcodes in ascending colon LN (BC.2557) and an intercostal LN (BC.1012) but not in rebound viraemia. Asc. colon, ascending colon. c, LV3 had two distinct viral plasma rebound barcode lineages (BC.2431 and BC.1136), of which BC.2431 was also identified as a vRNA expression outlier in a mesenteric LN, linking this distinct tissue site with rebound plasma viraemia. d, From LV4, four detectable barcode lineages were observed in rebound viraemia (BC.5385, BC.1872, BC.213 and BC.834), three of which were also vRNA expression outliers in one or two tissues. Trans. colon, transverse colon; Desc. colon, descending colon. e, LV5 had three detectable plasma rebound barcode lineages; of these, two (BC.3338 and BC.1078) were also found as vRNA expression outliers in a descending colon LN and in an ileocaecal LN, respectively. Although barcode 401 (purple) was not identified in rebound plasma, it was enriched within the same ileocaecal LN sample that gave rise to BC.1078. f, VL6 had five detectable rebounding viral lineages in plasma; two of these rebounding lineages (BC.8128 (orange) and BC.4406 (green)) were also found as vRNA expression outliers within a transverse colon LN and in a mesocolic LN, respectively. One additional rebounding lineage (BC.3963; blue) was the dominant lineage in rebound plasma and was found enriched in four distinct GI tract and GI tract-draining LNs. Two additional barcode lineages (BC.662 (purple) and BC.2567 (red)) were not found in rebound plasma but were identified as vRNA expression outliers in transverse colon and in three sites in the GI tract and GI tract-draining LNs, respectively. The frequency of all tissue barcodes that were vDNA⁺/vRNA⁺ ranged from 10% to 18%. Blue lines with shaded area delineate the 99% PI.

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