{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,22]],"date-time":"2026-03-22T02:08:26Z","timestamp":1774145306644,"version":"3.50.1"},"reference-count":17,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,9,16]],"date-time":"2022-09-16T00:00:00Z","timestamp":1663286400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Several flaviviruses such as Hepatitis C virus, West Nile virus, Dengue virus and Japanese Encephalitis virus exploit the raft platform to enter host cells whereas the involvement of lipid rafts in Zika virus\u2013host cell interaction has not yet been demonstrated. Zika virus disease is caused by a flavivirus transmitted by Aedes spp. Mosquitoes, although other mechanisms such as blood transfusion, sexual and maternal\u2013fetal transmission have been demonstrated. Symptoms are generally mild, such as fever, rash, joint pain and conjunctivitis, but neurological complications, including Guillain-Barr\u00e9 syndrome, have been associated to this viral infection. During pregnancy, it can cause microcephaly and other congenital abnormalities in the fetus, as well as pregnancy complications, representing a serious health threat. In this study, we show for the first time that Zika virus employs cell membrane lipid rafts as a portal of entry into Vero cells. We previously demonstrated that the antifungal drug Amphotericin B (AmphB) hampers a microbe\u2013host cell interaction through the disruption of lipid raft architecture. Here, we found that Amphotericin B by the same mechanism of action inhibits both Zika virus cell entry and replication. These data encourage further studies on the off-label use of Amphotericin B in Zika virus infections as a new and alternate antiviral therapy.<\/jats:p>","DOI":"10.3390\/v14092059","type":"journal-article","created":{"date-parts":[[2022,9,21]],"date-time":"2022-09-21T00:08:09Z","timestamp":1663718889000},"page":"2059","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Zika Virus Exploits Lipid Rafts to Infect Host Cells"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7852-2739","authenticated-orcid":false,"given":"Daniela","family":"Peruzzu","sequence":"first","affiliation":[{"name":"Center for Gender Specific Medicine, Istituto Superiore di Sanit\u00e0, Viale Regina Elena 299, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonello","family":"Amendola","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Istituto Superiore di Sanit\u00e0, Viale Regina Elena 299, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9078-8350","authenticated-orcid":false,"given":"Giulietta","family":"Venturi","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Istituto Superiore di Sanit\u00e0, Viale Regina Elena 299, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0872-185X","authenticated-orcid":false,"given":"Valeria","family":"de Turris","sequence":"additional","affiliation":[{"name":"Istituto Italiano di Tecnologia, CLN2S-Nanotechnology for Neuroscience, Viale Regina Elena 291, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giulia","family":"Marsili","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Istituto Superiore di Sanit\u00e0, Viale Regina Elena 299, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Fortuna","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Istituto Superiore di Sanit\u00e0, Viale Regina Elena 299, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katia","family":"Fecchi","sequence":"additional","affiliation":[{"name":"Center for Gender Specific Medicine, Istituto Superiore di Sanit\u00e0, Viale Regina Elena 299, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Cristina","family":"Gagliardi","sequence":"additional","affiliation":[{"name":"Center for Gender Specific Medicine, Istituto Superiore di Sanit\u00e0, Viale Regina Elena 299, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1038\/nri1129","article-title":"Pathogens: Raft hijackers","volume":"3","year":"2003","journal-title":"Nat. Rev. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1042\/BC20090138","article-title":"Host-cell lipid rafts: A safe door for micro-organisms?","volume":"102","author":"Vieira","year":"2010","journal-title":"Biol. Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/35036052","article-title":"Lipid rafts and signal transduction","volume":"1","author":"Simons","year":"2000","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1128\/MMBR.67.2.226-237.2003","article-title":"Virus Entry, Assembly, Budding, and Membrane Rafts","volume":"67","author":"Chazal","year":"2003","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"245090","DOI":"10.1155\/2011\/245090","article-title":"Function of Membrane Rafts in Viral Lifecycles and Host Cellular Response","volume":"2011","author":"Takahashi","year":"2011","journal-title":"Biochem. Res. Int."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1038\/s41564-020-0714-0","article-title":"The continued threat of emerging flaviviruses","volume":"5","author":"Pierson","year":"2020","journal-title":"Nat. Microbiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.3201\/eid2207.151990","article-title":"A Literature Review of Zika Virus","volume":"22","author":"Plourde","year":"2016","journal-title":"Emerg. Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2099","DOI":"10.1016\/S0140-6736(17)31450-2","article-title":"An update on Zika virus infection","volume":"390","author":"Baud","year":"2017","journal-title":"Lancet"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1001\/jamaneurol.2018.1058","article-title":"Clinical Features of Guillain-Barr\u00e9 Syndrome With vs Without Zika Virus Infection, Puerto Rico, 2016","volume":"75","author":"Dirlikov","year":"2018","journal-title":"JAMA Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"S875","DOI":"10.1093\/infdis\/jix396","article-title":"Modes of Transmission of Zika Virus","volume":"216","author":"Gregory","year":"2017","journal-title":"J. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"695106","DOI":"10.3389\/fncel.2021.695106","article-title":"Zika Virus and Neuropathogenesis: The Unanswered Question of Which Strain Is More Prone to Causing Microcephaly and Other Neurological Defects","volume":"15","author":"King","year":"2021","journal-title":"Front. Cell. Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"388","DOI":"10.3389\/fcimb.2018.00388","article-title":"The Role of Host Cholesterol During Flavivirus Infection","volume":"8","year":"2018","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.3201\/eid1408.080287","article-title":"Genetic and serologic properties of Zika virus associated with an epidemic, Yap State, Micronesia, 2007","volume":"14","author":"Lanciotti","year":"2008","journal-title":"Emerg. Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4066","DOI":"10.1128\/JCM.38.11.4066-4071.2000","article-title":"Rapid detection of west nile virus from human clinical specimens, field-collected mosquitoes, and avian samples by a TaqMan reverse transcriptase-PCR assay","volume":"38","author":"Lanciotti","year":"2000","journal-title":"J. Clin. Microbiol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"de Turris, V., Teloni, R., Chiani, P., Bromuro, C., Mariotti, S., Pardini, M., Nisini, R., Torosantucci, A., and Gagliardi, M.C. (2015). Candida albicans Targets a Lipid Raft\/Dectin-1 Platform to Enter Human Monocytes and Induce Antigen Specific T Cell Responses. 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