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Noghero, A.

Publications and source records attributed to Noghero, A..

2 recordsLinked to original sources

Cargo and biological properties of extracellular vesicles released from human adenovirus type 4-infected lung epithelial cells

Extracellular vesicles (EVs) are rapidly gaining recognition as critical mediators of inter-cellular communication during viral infections. To contribute to fill the gap in knowledge regarding the role of EVs in adenovirus infection, we used human adenovirus type 4 of species Mastadenovirus exoticum (HAdV-E4), a prevalent respiratory and ocular pathogen, and characterized the cargo and biological properties of EVs released by HAdV-E4-infected A549 lung epithelial cells at a pre-lytic stage of infection. Using immunocapture-based isolation and multi-omics approaches, we found that infection profoundly alters the EV uploaded proteome and small non-coding RNA repertoire. Mass spectrometry identified 268 proteins unique to EVs purified from infected cells (AdV-EVs), with enrichment in pathways supporting vesicle trafficking and viral protein translation, and importantly also a few virus-encoded proteins. Small RNA transcriptome analysis showed differential uploading in AdV-EVs of various small non-coding RNAs, including snoRNAs, as well as the presence of virus associated RNAs I and II. Notably, AdV-EVs contained viral genomic DNA and were capable of initiating productive infection upon delivery to naive cells in the absence of detectable viral particles. Our data suggest that EVs released during HAdV-E4 infection may serve as vehicles for non-lytic viral dissemination and highlight their possible role in intra-host dissemination.

microbiology↗

Identification of HIV Tat and NF-κB binding proteins associated with semen-derived extracellular vesicles

Semen-derived extracellular vesicles (SEVs) have been shown to inhibit transactivation of the long terminal repeat (LTR) in human immunodeficiency virus type 1 (HIV-1, or HIV) and, hence, viral replication by blocking the interaction of the viruss transcriptional activator Tat and host transcription factors NF-{kappa}B and Sp1. The ability of SEVs to regulate the activities of transcription factors suggests that SEVs may contain transcription activators and repressors. Here, we identified host proteins in human SEVs that interacted with the Tat and NF-{kappa}B subunit p65. Integrative network and pathway enrichment analyses of these complexes revealed associations with an array of biological functions regulating genome transcription. In particular, several proteins in SEVs could bind to both Tat and NF-{kappa}B: the scaffolding and cell signaling regulatory protein AKAP9, the G protein signaling regulator ARHGEF28, the small nuclear RNA processor INTS1, the epigenetic reader BRD2, and the transcription elongation inhibitor NELFB. NF-{kappa}B p65-bound NELFB also interacted with HEXIM1, another transcription elongation inhibitor, suggesting that SEVs may inhibit HIV propagation through networks of transcriptional regulation and repression. One Sentence SummaryProteins in vesicles shed from human semen may repress HIV by targeting transcription factors.

molecular biology↗