{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T15:46:43Z","timestamp":1791215203896,"version":"4.1.0"},"reference-count":54,"publisher":"American Society for Microbiology","issue":"14","license":[{"start":{"date-parts":[[2008,7,15]],"date-time":"2008-07-15T00:00:00Z","timestamp":1216080000000},"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":[[2008,7,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Human immunodeficiency virus type 1 (HIV-1) infection has been implicated in impairing various aspects of NK cell function in viremic condition, and several viral factors contribute to these defects. Here, we evaluated the effect of HIV-1 Vpr on NK cell cytolytic function and cytokine (gamma interferon [IFN-\u03b3]) production in the context of infection and exposure. Our data indicate that NK cells derived from a peripheral blood mononuclear cell culture infected in vitro with HIV-1 vpr(+) virus or exposed to recombinant Vpr protein exhibited reduced target cell killing in conjunction with diminished expression of CD107a and reduced IFN-\u03b3 production compared to their Vpr-negative counterparts. This Vpr-induced NK cell defect is in part through differential regulation of interleukin-12 and transforming growth factor \u03b2 production by the infected target cells and concomitant activation of Smad3 signaling pathway. Collectively, these results illustrate the ability of Vpr to impair NK cell-mediated innate immune functions indirectly by dysregulating multiple cytokines in the infected target cells, thus increasing disease severity and affecting the final outcome in HIV-1 infection.<\/jats:p>","DOI":"10.1128\/jvi.01979-07","type":"journal-article","created":{"date-parts":[[2008,4,17]],"date-time":"2008-04-17T01:10:29Z","timestamp":1208394629000},"page":"7189-7200","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":19,"title":["Infection with Vpr-Positive Human Immunodeficiency Virus Type 1 Impairs NK Cell Function Indirectly through Cytokine Dysregulation of Infected Target Cells"],"prefix":"10.1128","volume":"82","author":[{"given":"Biswanath","family":"Majumder","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases and Microbiology, University of Pittsburgh Graduate School of Public Health, 130 Desoto Street, Pittsburgh, Pennsylvania 15261"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narasimhan J.","family":"Venkatachari","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Microbiology, University of Pittsburgh Graduate School of Public Health, 130 Desoto Street, Pittsburgh, Pennsylvania 15261"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaylee","family":"O'Leary","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Microbiology, University of Pittsburgh Graduate School of Public Health, 130 Desoto Street, Pittsburgh, Pennsylvania 15261"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Velpandi","family":"Ayyavoo","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Microbiology, University of Pittsburgh Graduate School of Public Health, 130 Desoto Street, Pittsburgh, Pennsylvania 15261"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-199602000-00003"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.8.5305"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.aids.0000237371.31315.48"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-03-1100"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.11.5764"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1086\/429300"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.5.3362"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00887-07"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.0030043"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20051143"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.82125-0"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.1999.tb01283.x"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1711"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.69.11.6705-6711.1995"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1097\/00042560-199511000-00005"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0705397"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.80.8.3985-3993.2006"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1086\/368222"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.2.1107"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1086\/382090"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/83130"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2006.05.002"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.13.7990-8003.2005"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00893-06"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2336091100"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0409872102"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20060894"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.19.12365-12374.2005"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.aids.0000183632.12418.33"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.169.11.6361"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2006.02.008"},{"key":"e_1_3_2_33_2","first-page":"103","volume":"17","year":"2005","unstructured":"Muthumani, K., D. 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