{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T17:10:21Z","timestamp":1780333821806,"version":"3.54.1"},"reference-count":77,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,2,15]],"date-time":"2022-02-15T00:00:00Z","timestamp":1644883200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Marie Sk\u0142odowska-Curie action CORVOS EU-H2020-MSCA-ITN-2019","award":["860064"],"award-info":[{"award-number":["860064"]}]},{"DOI":"10.13039\/501100002428","name":"FWF Austrian Science Fund","doi-asserted-by":"publisher","award":["P33510-B"],"award-info":[{"award-number":["P33510-B"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Nonadjacent immune cells communicate through a complex network of tunneling nanotubes (TNTs). TNTs can be hijacked by HIV-1, allowing it to spread between connected cells. Dendritic cells (DCs) are among the first cells to encounter HIV-1 at mucosal sites, but they are usually efficiently infected only at low levels. However, HIV-1 was demonstrated to productively infect DCs when the virus was complement-opsonized (HIV-C). Such HIV-C-exposed DCs mediated an improved antiviral and T-cell stimulatory capacity. The role of TNTs in combination with complement in enhancing DC infection with HIV-C remains to be addressed. To this aim, we evaluated TNT formation on the surface of DCs or DC\/CD4+ T-cell co-cultures incubated with non- or complement-opsonized HIV-1 (HIV, HIV-C) and the role of TNTs or locally produced complement in the infection process using either two different TNT or anaphylatoxin receptor antagonists. We found that HIV-C significantly increased the formation of TNTs between DCs or DC\/CD4+ T-cell co-cultures compared to HIV-exposed DCs or co-cultures. While augmented TNT formation in DCs promoted productive infection, as was previously observed, a significant reduction in productive infection was observed in DC\/CD4+ T-cell co-cultures, indicating antiviral activity in this setting. As expected, TNT inhibitors significantly decreased infection of HIV-C-loaded-DCs as well as HIV- and HIV-C-infected-DC\/CD4+ T-cell co-cultures. Moreover, antagonizing C5aR significantly inhibited TNT formation in DCs as well as DC\/CD4+ T-cell co-cultures and lowered the already decreased productive infection in co-cultures. Thus, local complement mobilization via DC stimulation of complement receptors plays a pivotal role in TNT formation, and our findings herein might offer an exciting opportunity for novel therapeutic approaches to inhibit trans infection via C5aR targeting.<\/jats:p>","DOI":"10.3390\/biom12020313","type":"journal-article","created":{"date-parts":[[2022,2,15]],"date-time":"2022-02-15T22:43:22Z","timestamp":1644965002000},"page":"313","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["HIV-1 Trans Infection via TNTs Is Impeded by Targeting C5aR"],"prefix":"10.3390","volume":"12","author":[{"given":"Giulia","family":"Bertacchi","sequence":"first","affiliation":[{"name":"Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8955-7654","authenticated-orcid":false,"given":"Wilfried","family":"Posch","sequence":"additional","affiliation":[{"name":"Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5888-5118","authenticated-orcid":false,"given":"Doris","family":"Wilflingseder","sequence":"additional","affiliation":[{"name":"Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,15]]},"reference":[{"key":"ref_1","unstructured":"Joint United Nations Programme on HIV\/AIDS (2021). 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