{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T01:42:02Z","timestamp":1788486122899,"version":"build-2803163510"},"reference-count":100,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,3,29]],"date-time":"2024-03-29T00:00:00Z","timestamp":1711670400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"Intramural Research Program of the National Cancer Institute, National Institutes of Health","doi-asserted-by":"publisher","award":["HHSN26120080001E"],"award-info":[{"award-number":["HHSN26120080001E"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>The transient depletion of monocytes alone prior to exposure of macaques to HTLV-1 enhances both HTLV-1WT (wild type) and HTLV-1p12KO (Orf-1 knockout) infectivity, but seroconversion to either virus is not sustained over time, suggesting a progressive decrease in virus expression. These results raise the hypotheses that either HTLV-1 persistence depends on a monocyte reservoir or monocyte depletion provides a transient immune evasion benefit. To test these hypotheses, we simultaneously depleted NK cells, CD8+ T cells, and monocytes (triple depletion) prior to exposure to HTLV-1WT or HTLV-1p12KO. Remarkably, triple depletion resulted in exacerbation of infection by both viruses and complete rescue of HTLV-1p12KO infectivity. Following triple depletion, we observed rapid and sustained seroconversion, high titers of antibodies against HTLV-1 p24Gag, and frequent detection of viral DNA in the blood and tissues of all animals when compared with depletion of only CD8+ and NK cells, or monocytes alone. The infection of macaques with HTLV-1WT or HTLV-1p12KO was associated with higher plasma levels of IL-10 after 21 weeks, while IL-6, IFN-\u03b3, IL-18, and IL-1\u03b2 were only elevated in animals infected with HTLV-1WT. The repeat depletion of monocytes, NK, and CD8+ cells seven months following the first exposure to HTLV-1 did not further exacerbate viral replication. These results underscore the contribution of monocytes in orchestrating anti-viral immunity. Indeed, the absence of orf-1 expression was fully compensated by the simultaneous depletion of CD8+ T cells, NK cells, and monocytes, underlining the primary role of orf-1 in hijacking host immunity.<\/jats:p>","DOI":"10.3390\/pathogens13040292","type":"journal-article","created":{"date-parts":[[2024,3,31]],"date-time":"2024-03-31T13:39:37Z","timestamp":1711892377000},"page":"292","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Complete Rescue of HTLV-1p12KO Infectivity by Depletion of Monocytes Together with NK and CD8+ T Cells"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9873-6432","authenticated-orcid":false,"given":"Anna","family":"Gutowska","sequence":"first","affiliation":[{"name":"Animal Models and Retroviral Vaccines Section, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarkis","family":"Sarkis","sequence":"additional","affiliation":[{"name":"Animal Models and Retroviral Vaccines Section, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6120-8943","authenticated-orcid":false,"given":"Mohammad Arif","family":"Rahman","sequence":"additional","affiliation":[{"name":"Animal Models and Retroviral Vaccines Section, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine C.","family":"Goldfarbmuren","sequence":"additional","affiliation":[{"name":"Vaccine Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA"},{"name":"Advanced Biomedical Computational Science, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramona","family":"Moles","sequence":"additional","affiliation":[{"name":"Animal Models and Retroviral Vaccines Section, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3455-3992","authenticated-orcid":false,"given":"Massimiliano","family":"Bissa","sequence":"additional","affiliation":[{"name":"Animal Models and Retroviral Vaccines Section, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melvin","family":"Doster","sequence":"additional","affiliation":[{"name":"Animal Models and Retroviral Vaccines Section, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robyn","family":"Washington-Parks","sequence":"additional","affiliation":[{"name":"Animal Models and Retroviral Vaccines Section, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"McKinnon","sequence":"additional","affiliation":[{"name":"Vaccine Branch Flow Cytometry Core, National Cancer Institute, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabela","family":"Silva de Castro","sequence":"additional","affiliation":[{"name":"Animal Models and Retroviral Vaccines Section, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Schifanella","sequence":"additional","affiliation":[{"name":"Animal Models and Retroviral Vaccines Section, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genoveffa","family":"Franchini","sequence":"additional","affiliation":[{"name":"Animal Models and Retroviral Vaccines Section, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia A.","family":"Pise-Masison","sequence":"additional","affiliation":[{"name":"Animal Models and Retroviral Vaccines Section, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7415","DOI":"10.1073\/pnas.77.12.7415","article-title":"Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma","volume":"77","author":"Poiesz","year":"1980","journal-title":"Proc. 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