Profiling HIV1-host protein-protein interaction networks in patient-derived exosome proteins: impact on pathophysiology and innate immune pathways.

Abstract

Objectives: The objective of this research is to investigate the pathophysiological progression of HIV from acute infection to chronic immunodeficiency (AIDS) and to understand the host's immunological responses, which are pivotal for elucidating disease aetiology and optimizing antiretroviral therapy (ART). Additionally, the study aims to explore the role of exosomes (40-130 nm bilipid-layered vesicles released by nearly all cell types) as key mediators of intercellular communication in the context of HIV infection.

Materials and methods: Recent research has uncovered that cells infected with HIV-1 release exosomes carrying a mix of viral and host components such as proteins, nucleic acids, lipids, and other metabolites. To decipher the plausible role of exosome-derived proteins in HIV disease progression, the exosomes isolated from HIV patient's serum were subjected to LC-MS/MS analysis to identify exosome-derived human and viral protein sequences. The identified proteins were then investigated, annotated, and explored for protein-protein interaction (PPI) network between HIV and the human host's proteins. Earlier experimental efforts focused on identifying PPI networks in host cells or only within the virus.

Results: The analysis showed that out of twelve exosome-derived host proteins identified from HIV-1 patient's samples, only five of the proteins were associated with Toll-like receptors (TLR), inflammasome-activation, inhibition of apoptosis, innate immune response modulation, and autophagy pathways. In the TLR pathway, CDH5, ENO1, OGT, TJP1, and TRAF6 exosome-derived host proteins participated in regulation. Notably, CDH5, ENO1, OGT, and TRAF6 were shared among these pathways, BioGRID version 4.4 showed that HIV-1 Gag, Gag-pol, Env, and Nef proteins interact with 196, 162, 158, and 80 human proteins, respectively, associated with different innate immune response pathways.

Conclusion: These findings are a step ahead in comprehending the pathophysiology of HIV1 and the innate immune response pathways, providing excellent opportunities to explore further exosome-based biomarkers for theranostic approaches.