Fig. 4. In vivo distribution of exosome cargo and ZPAMt exosome mediated suppression of viral load in HIV-1-infected hu-PBMC-NSG mice.

a Schematic illustrating the experimental plan to check the efficacy of ZPAMt exosomes in controlling HIV-1 infection progression in hu-PBMC-NSG mice. b Dynamics of viremia levels in hu-PBMC-NSG mice after treatment with either nLuc exosomes (left), ZFP exosomes (center), ZPAMt exosomes (right) over a course of 10 weeks of infection and treatment as measured by RT-qPCR. The trendline in red indicates the median of the viral load. The pink line indicates the limit of detection (LOD) of the PCR assay is 200 RNA copies/ml in 50–80 μl of mice plasma. c Median values of HIV-1 load monitored periodically in hu-PBMC NSG mice subjected to different treatments i.e. 4 weeks (w) oral cART, 2w oral cART + nLuc or ZFP or ZPAMt exosomes, and no cART mice. Greyline indicates LOD. d MeDIP assay revealed the status of DNA methylation as an effect of treatment of nLuc/ZFP/ZPAMt exosomes on BM-derived cells from HIV-1-infected hu-PBMC-NSG mice. e Toxicity assay was done by measuring Alanine transaminase activity (left) and Aspartate aminotransferase assay activity (right) for all the mice and was compared to activity from untreated NSG mice. Ordinary one-way ANOVA was used to calculate significance P > 0.05 is nonsignificant (ns). In b–e n = 6 was used for nLuc and ZFP treated mice, n = 7 was used for ZPAMt treated mice and in (c, e) n = 3 was used for oral cART treated, no cART, hu-PBMC NSG, and untreated NSG. For b, e P value was determined by the Kruskal–Wallis test followed by Dunn’s post hoc test for multiple comparisons. Source data are provided in the source data file.