{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T18:39:16Z","timestamp":1791398356466,"version":"4.3.3"},"reference-count":38,"publisher":"American Society for Microbiology","issue":"13","license":[{"start":{"date-parts":[[2015,7,1]],"date-time":"2015-07-01T00:00:00Z","timestamp":1435708800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2015,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Recent evidence suggests that even in treated infections, human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) replication may continue in lymph nodes (LN), serving as a potential virus reservoir. Here we investigated the effects of lentivirus infection on natural killer (NK) cell frequencies, phenotypes, and functions in naive and acutely or chronically SIVmac239-infected rhesus macaques. Compared to that in naive animals, we observed a 3-fold-greater frequency of cytotoxic CD16\n                    <jats:sup>+<\/jats:sup>\n                    CD56\n                    <jats:sup>\u2212<\/jats:sup>\n                    NK cells in LN of chronically infected macaques. However, NK cells did not appear to be trafficking to LN, as homing markers CD62L and CCR7 did not increase on circulating NK cells during infection. LN NK cells demonstrated enhanced cytotoxicity in acute infection, with 2-fold increases in perforin expression and 3-fold increases in CD107a expression following mitogen stimulation. Lysis of K562 cells by LN NK cells from acutely infected animals was greater than lysis by preinfection samples from the same animals. LN NK cells from chronically infected animals lysed K562 cells more efficiently than LN NK cells from uninfected animals, but importantly, surrogate markers of cytotoxicity in infected macaques were disproportionately greater than\n                    <jats:italic>ex vivo<\/jats:italic>\n                    killing. Furthermore, Tim-3, an indicator of activation and\/or exhaustion, was upregulated 3-fold on LN NK cells in chronically infected animals. Collectively, these data suggest that LN NK cells are skewed toward a cytotoxic phenotype during SIV infection but may become dysfunctional and exhausted in chronic disease.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>IMPORTANCE<\/jats:bold>\n                    The accumulation of CD16\n                    <jats:sup>+<\/jats:sup>\n                    CD56\n                    <jats:sup>\u2212<\/jats:sup>\n                    NK cells in the SIV-infected lymph node without changes in NK homing to the LN could suggest that these cells are differentiating\n                    <jats:italic>in situ<\/jats:italic>\n                    . Surprisingly, this increase in frequency of the cytotoxic subset of NK cells is not accompanied by an increase of similar magnitude in the cytolytic function of LN lymphocytes. This functional modulation, together with the higher Tim-3 expression observed on LN NK cells isolated from chronically infected animals than on those from naive macaques, is indicative of an exhausted phenotype. This exhaustion could contribute to the robust replication of HIV and SIV in the LN during acute and chronic stages of infection, allowing the survival of infected cells and maintenance of a viral reservoir.\n                  <\/jats:p>","DOI":"10.1128\/jvi.00660-15","type":"journal-article","created":{"date-parts":[[2015,4,22]],"date-time":"2015-04-22T22:32:19Z","timestamp":1429741939000},"page":"6887-6894","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":53,"title":["Accumulation of Cytotoxic CD16\n                    <sup>+<\/sup>\n                    NK Cells in Simian Immunodeficiency Virus-Infected Lymph Nodes Associated with\n                    <i>In Situ<\/i>\n                    Differentiation and Functional Anergy"],"prefix":"10.1128","volume":"89","author":[{"given":"Jamie L.","family":"Schafer","sequence":"first","affiliation":[{"name":"Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiying","family":"Li","sequence":"additional","affiliation":[{"name":"Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tristan I.","family":"Evans","sequence":"additional","affiliation":[{"name":"New England Primate Research Center, Harvard Medical School, Southborough, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob D.","family":"Estes","sequence":"additional","affiliation":[{"name":"AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory, Frederick, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Keith","family":"Reeves","sequence":"additional","affiliation":[{"name":"Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA"},{"name":"New England Primate Research Center, Harvard Medical School, Southborough, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng934"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng2035"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10237"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-02-0696"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80065-5"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-06-028175"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000613"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000101"},{"key":"e_1_3_2_10_2","doi-asserted-by":"crossref","first-page":"6433","DOI":"10.4049\/jimmunol.161.11.6433","article-title":"Natural killer cells from HIV-1+ patients produce C-C chemokines and inhibit HIV-1 infection","volume":"161","author":"Fehniger TA","year":"1998","unstructured":"Fehniger TA, Herbein G, Yu H, Para MI, Bernstein ZP, O'Brien WA, Caligiuri MA. 1998. Natural killer cells from HIV-1+ patients produce C-C chemokines and inhibit HIV-1 infection. J Immunol 161:6433\u20136438.","journal-title":"J Immunol"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-03-1100"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01126-10"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-01-265595"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0409872102"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0056309"},{"key":"e_1_3_2_16_2","first-page":"428","article-title":"Evidence for a defect of antibody-dependent cellular cytotoxic (ADCC) effector function and anti-HIV gp120\/41-specific ADCC-mediating antibody titres in HIV-infected individuals","volume":"7","author":"Ahmad A","year":"1994","unstructured":"Ahmad A, Morisset R, Thomas R, Menezes J. 1994. Evidence for a defect of antibody-dependent cellular cytotoxic (ADCC) effector function and anti-HIV gp120\/41-specific ADCC-mediating antibody titres in HIV-infected individuals. J Acquir Immune Defic Syndr 7:428\u2013437.","journal-title":"J Acquir Immune Defic Syndr"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.11.5764"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200635901"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2012.00417"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201040886"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.21.9838"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002048"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm880"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.8.4938-4949.2003"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02497-12"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.1.690"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-06-437608"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1401161"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1318249111"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000296"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiu671"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004551"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0000000000000589"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-11-392951"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1186\/1742-4690-10-74"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1400961"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002984"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-13-0171"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature13848"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.00660-15","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.00660-15","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,9]],"date-time":"2023-08-09T14:38:43Z","timestamp":1691591923000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/JVI.00660-15"}},"subtitle":[],"editor":[{"given":"G.","family":"Silvestri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2015,7]]},"references-count":38,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2015,7]]}},"alternative-id":["10.1128\/JVI.00660-15"],"URL":"https:\/\/doi.org\/10.1128\/jvi.00660-15","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,7]]},"assertion":[{"value":"2015-03-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-04-14","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-06-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}