https://orcid.org/0000-0002-1511-8576
Figures & data
Figure 1. Model of chronic inflammation enhanced by extracellular vesicles.
HIV replication or expression of viral components in latently infected cells, in conjunction with bacterial PAMPs released into circulation as a consequence of microbial translocation in the gut, constitute a persistent activating stimuli for immune cells such as T lymphocytes, monocytes and macrophages [Citation1]. These activated cells release into circulation EVs containing pro-inflammatory molecules from the host or HIV-derived PAMPs (as detailed in the enlarged vesicle) [Citation2]. Macrophages exposed to circulating EVs become activated and release inflammatory cytokines [Citation3], which in turn contribute to a positive loop of systemic chronic inflammation [Citation4].
![Figure 1. Model of chronic inflammation enhanced by extracellular vesicles.HIV replication or expression of viral components in latently infected cells, in conjunction with bacterial PAMPs released into circulation as a consequence of microbial translocation in the gut, constitute a persistent activating stimuli for immune cells such as T lymphocytes, monocytes and macrophages [Citation1]. These activated cells release into circulation EVs containing pro-inflammatory molecules from the host or HIV-derived PAMPs (as detailed in the enlarged vesicle) [Citation2]. Macrophages exposed to circulating EVs become activated and release inflammatory cytokines [Citation3], which in turn contribute to a positive loop of systemic chronic inflammation [Citation4].](/cms/asset/bb978835-fa5c-48f2-8e05-20f836ff31ad/zjev_a_1687275_f0001_oc.jpg)
Figure 2. Proposed role of HIF-1α in the inflammatory effects in HIV infection.
HIV-1 infection of CD4 + T cells [Citation1] triggers HIF-1α activity, which promotes the transcription of Rab22a and Rab27a [Citation2], thus favouring intracellular trafficking routes involved in EV secretion [Citation3]. Released EVs, in turn, promote HIF-1α activity in target cells [Citation4], probably by delivering HIF-1α protein, or a lncRNA that stabilizes HIF-1α mRNA by preventing its degradation. Induction of HIF-1α in EV-recipient CD4 + T cells and macrophages is required for secretion of pro-inflammatory cytokines [Citation5]. Thus, HIF-1α and EVs coordinately promote inflammation during HIV infection.
![Figure 2. Proposed role of HIF-1α in the inflammatory effects in HIV infection.HIV-1 infection of CD4 + T cells [Citation1] triggers HIF-1α activity, which promotes the transcription of Rab22a and Rab27a [Citation2], thus favouring intracellular trafficking routes involved in EV secretion [Citation3]. Released EVs, in turn, promote HIF-1α activity in target cells [Citation4], probably by delivering HIF-1α protein, or a lncRNA that stabilizes HIF-1α mRNA by preventing its degradation. Induction of HIF-1α in EV-recipient CD4 + T cells and macrophages is required for secretion of pro-inflammatory cytokines [Citation5]. Thus, HIF-1α and EVs coordinately promote inflammation during HIV infection.](/cms/asset/56454a74-515b-410e-a8f7-d0749d369aa4/zjev_a_1687275_f0002_oc.jpg)
