{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T06:01:01Z","timestamp":1785564061755,"version":"3.56.0"},"reference-count":62,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T00:00:00Z","timestamp":1765324800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007061","name":"Secretar\u00eda Nacional de Ciencia, Tecnolog\u00eda e Innovaci\u00f3n de Panam\u00e1","doi-asserted-by":"publisher","award":["FIED21-004"],"award-info":[{"award-number":["FIED21-004"]}],"id":[{"id":"10.13039\/501100007061","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation","doi-asserted-by":"crossref","award":["2023\/01641-1"],"award-info":[{"award-number":["2023\/01641-1"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Sistema Nacional de Investigaci\u00f3n de Panam\u00e1"},{"DOI":"10.13039\/501100003593","name":"National Council for Scientific and Technological Development","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Indiana University"},{"name":"Gorgas Memorial Institute for Health Studies"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Leishmania RNA virus 1 (LRV-1) is a double-stranded RNA virus identified in several Leishmania spp. LRV-1 has been associated with increased disease severity and therapeutic failure in cutaneous leishmaniasis (CL). Although LRV-1 has been reported in the Americas, its influence on parasite infectivity and host immune responses remains poorly characterized in Panamanian isolates. In this study, we investigate the in vitro infectivity and immunomodulatory effects of LRV-1-positive (LRV-1+) versus LRV-1-negative (LRV-1\u2212) isolates of Leishmania (Viannia), including clinical strains of L. (V.) panamensis and L. (V.) guyanensis. A total of 21 isolates (nine LRV-1+, nine LRV-1\u2212, and three reference strains) were used to infect human U937 macrophages. The infectivity index (II) was measured at 24, 48, and 72 h post-infection. Cytokine levels of TNF-\u03b1, IFN-\u03b3, IL-4, IL-6, IL-10, and IL-17 were quantified by flow cytometry, and IL-1\u03b2 by ELISA at 24 and 48 h. LRV-1+ isolates exhibited significantly higher infectivity at 48 h (mean II = 1386.2) and 72 h (mean II = 1316.8) compared to LRV-1\u2212 isolates (mean II = 714.4 and 571.0, respectively; p &lt; 0.001). Two L. (V.) panamensis LRV-1+ isolates associated with complicated CL cases displayed the highest II values. Cytokine analysis revealed that LRV-1+ isolates induced elevated TNF-\u03b1 (p &lt; 0.01) and IL-1\u03b2 (p &lt; 0.001), along with reduced IFN-\u03b3 (p &lt; 0.01), while no significant differences were observed for IL-4, IL-6, IL-10, or IL-17. These findings indicate that LRV-1 enhances parasite infectivity and promotes a pro-inflammatory cytokine profile, which may contribute to disease persistence and treatment failure.<\/jats:p>","DOI":"10.3390\/pathogens14121263","type":"journal-article","created":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T14:22:40Z","timestamp":1765376560000},"page":"1263","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Leishmaniavirus Type 1 Enhances In Vitro Infectivity and Modulates the Immune Response to Leishmania (Viannia) Isolates"],"prefix":"10.3390","volume":"14","author":[{"given":"Armando A.","family":"Bonilla Fong","sequence":"first","affiliation":[{"name":"Programa de Maestr\u00eda en Ciencias Parasitol\u00f3gicas, Facultad de Ciencias Naturales, Exactas y Tecnolog\u00eda, Universidad de Panam\u00e1, Panam\u00e1 0816-3366, Panama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2847-2419","authenticated-orcid":false,"given":"Vanessa J.","family":"Pineda","sequence":"additional","affiliation":[{"name":"Departamento de Investigaci\u00f3n en Parasitolog\u00eda, Instituto Conmemorativo Gorgas de Estudios de la Salud, Panam\u00e1 0816-02593, Panama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6669-4290","authenticated-orcid":false,"given":"Jos\u00e9 E.","family":"Calzada","sequence":"additional","affiliation":[{"name":"Departamento de Investigaci\u00f3n en Parasitolog\u00eda, Instituto Conmemorativo Gorgas de Estudios de la Salud, Panam\u00e1 0816-02593, Panama"},{"name":"Facultad de Medicina Veterinaria, Universidad de Panam\u00e1, Panam\u00e1 0816-3366, Panama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1080-2440","authenticated-orcid":false,"given":"Marcia Dalastra","family":"Laurenti","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Patologia de Mol\u00e9stias Infecciosas, Faculdade de Medicina, Universidade de S\u00e3o Paulo, S\u00e3o Paulo 01246-903, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5986-6381","authenticated-orcid":false,"given":"Luiz Felipe Domingues","family":"Passero","sequence":"additional","affiliation":[{"name":"Institute of Biosciences, S\u00e3o Paulo State University (UNESP), S\u00e3o Vicente 11330-900, SP, Brazil"},{"name":"Institute for Advanced Studies of Ocean, S\u00e3o Paulo State University (UNESP), S\u00e3o Vicente 11350-011, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3183-3753","authenticated-orcid":false,"given":"Davis","family":"Beltran","sequence":"additional","affiliation":[{"name":"Departamento de Investigaci\u00f3n en Virolog\u00eda y Biotecnolog\u00eda, Centro de Citometr\u00eda de Flujo, Instituto Conmemorativo Gorgas de Estudios de la Salud, Panam\u00e1 0816-02593, Panama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5301-2764","authenticated-orcid":false,"given":"Luis Fernando","family":"Chaves","sequence":"additional","affiliation":[{"name":"Department of Environmental and Occupational Health, School of Public Health-Bloomington, Bloomington, IN 47408, USA"},{"name":"Department of Geography, Indiana University, Bloomington, IN 47407, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5653-1332","authenticated-orcid":false,"given":"Azael","family":"Salda\u00f1a","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n y Diagn\u00f3stico de Enfermedades Parasitarias (CIDEP), Facultad de Medicina, Universidad de Panam\u00e1, Panam\u00e1 0816-3366, Panama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7297-1322","authenticated-orcid":false,"given":"Kadir","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Departamento de Investigaci\u00f3n en Parasitolog\u00eda, Instituto Conmemorativo Gorgas de Estudios de la Salud, Panam\u00e1 0816-02593, Panama"},{"name":"Departamento de Microbiolog\u00eda Humana, Facultad de Medicina, Universidad de Panam\u00e1, Panam\u00e1 0816-3366, Panama"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"9572","DOI":"10.1073\/pnas.85.24.9572","article-title":"LR1: A candidate RNA virus of Leishmania","volume":"85","author":"Tarr","year":"1988","journal-title":"Proc. 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