{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T21:55:28Z","timestamp":1787003728975,"version":"build-2736575974"},"reference-count":85,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T00:00:00Z","timestamp":1767571200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T00:00:00Z","timestamp":1767571200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/100000050","name":"U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL147715"],"award-info":[{"award-number":["R01HL147715"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL158316"],"award-info":[{"award-number":["R01HL158316"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL167655"],"award-info":[{"award-number":["R01HL167655"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI174269"],"award-info":[{"award-number":["R01AI174269"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Commun Biol"],"DOI":"10.1038\/s42003-025-09284-1","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T02:10:54Z","timestamp":1767579054000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["HIV disrupts the lung molecular clock, leading to lung inflammation and features of emphysema"],"prefix":"10.1038","volume":"9","author":[{"given":"Kingshuk","family":"Panda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyce Yao-chun","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria J.","family":"Santiago","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md. Sohanur","family":"Rahman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadiya Bi","family":"Shaikh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gagandeep","family":"Kaur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md Imam","family":"Faizan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khursheed Ul","family":"Islam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4524-6544","authenticated-orcid":false,"given":"Stephen M.","family":"Black","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5600-7314","authenticated-orcid":false,"given":"Christopher M.","family":"Evans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2274-2454","authenticated-orcid":false,"given":"Irfan","family":"Rahman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5633-9749","authenticated-orcid":false,"given":"Srinivasan","family":"Chinnapaiyan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5704-6876","authenticated-orcid":false,"given":"Hoshang J.","family":"Unwalla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,5]]},"reference":[{"key":"9284_CR1","unstructured":"Organization, W. H. World Health Statistics 2022: Monitoring Health for the SDGs. Sustainable Development Goals 7 (2022)."},{"key":"9284_CR2","doi-asserted-by":"publisher","first-page":"115","DOI":"10.20411\/pai.v8i2.665","volume":"8","author":"J Harper","year":"2023","unstructured":"Harper, J. et al. Progress note 2024: curing HIV; not in my lifetime or just around the corner? Pathog. Immun. 8, 115 (2023).","journal-title":"Pathog. Immun."},{"key":"9284_CR3","doi-asserted-by":"publisher","first-page":"2359","DOI":"10.3390\/ijerph19042359","volume":"19","author":"RA Roomaney","year":"2022","unstructured":"Roomaney, R. A., van Wyk, B. & Pillay-van Wyk, V. Aging with HIV: increased risk of HIV comorbidities in older adults. Int. J. Environ. Res. Public Health 19, 2359 (2022).","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"9284_CR4","doi-asserted-by":"publisher","first-page":"1120","DOI":"10.1093\/cid\/cir627","volume":"53","author":"G Guaraldi","year":"2011","unstructured":"Guaraldi, G. et al. Premature age-related comorbidities among HIV-infected persons compared with the general population. Clin. Infect. Dis. 53, 1120\u20131126 (2011).","journal-title":"Clin. Infect. Dis."},{"key":"9284_CR5","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1080\/17476348.2021.1848556","volume":"15","author":"K Byanova","year":"2021","unstructured":"Byanova, K., Kunisaki, K. M., Vasquez, J. & Huang, L. Chronic obstructive pulmonary disease in HIV. Expert Rev. Respir. Med. 15, 71\u201387 (2021).","journal-title":"Expert Rev. Respir. Med."},{"key":"9284_CR6","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1080\/07420520701535753","volume":"24","author":"CL Tsai","year":"2007","unstructured":"Tsai, C. L., Brenner, B. E. & Camargo, C. A. Jr Circadian-rhythm differences among emergency department patients with chronic obstructive pulmonary disease exacerbation. Chronobiol. Int. 24, 699\u2013713 (2007).","journal-title":"Chronobiol. Int."},{"key":"9284_CR7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12890-018-0755-9","volume":"19","author":"N Scichilone","year":"2019","unstructured":"Scichilone, N. et al. Circadian rhythm of COPD symptoms in clinically based phenotypes. Results from the STORICO Italian observational study. BMC Pulm. Med. 19, 1\u201313 (2019).","journal-title":"BMC Pulm. Med."},{"key":"9284_CR8","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.ejim.2017.05.021","volume":"43","author":"G Canonica","year":"2017","unstructured":"Canonica, G. et al. Characterization of circadian COPD symptoms by phenotype: methodology of the STORICO observational study. Eur. J. Intern. Med. 43, 62\u201368 (2017).","journal-title":"Eur. J. Intern. Med."},{"key":"9284_CR9","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1007\/s10928-021-09751-2","volume":"48","author":"VS Ayyar","year":"2021","unstructured":"Ayyar, V. S. & Sukumaran, S. Circadian rhythms: influence on physiology, pharmacology, and therapeutic interventions. J. Pharmacokin. Pharmacodyn. 48, 321\u2013338 (2021).","journal-title":"J. Pharmacokin. Pharmacodyn."},{"key":"9284_CR10","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1038\/s41392-022-00899-y","volume":"7","author":"F Fagiani","year":"2022","unstructured":"Fagiani, F. et al. Molecular regulations of circadian rhythm and implications for physiology and diseases. Signal Transduct. Target. Ther. 7, 41 (2022).","journal-title":"Signal Transduct. Target. Ther."},{"key":"9284_CR11","doi-asserted-by":"publisher","first-page":"16219","DOI":"10.1073\/pnas.1408886111","volume":"111","author":"R Zhang","year":"2014","unstructured":"Zhang, R., Lahens, N. F., Ballance, H. I., Hughes, M. E. & Hogenesch, J. B. A circadian gene expression atlas in mammals: implications for biology and medicine. Proc. Natl Acad. Sci. USA 111, 16219\u201316224 (2014).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"9284_CR12","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1146\/annurev-physiol-021909-135821","volume":"72","author":"C Dibner","year":"2010","unstructured":"Dibner, C., Schibler, U. & Albrecht, U. The mammalian circadian timing system: organization and coordination of central and peripheral clocks. Annu. Rev. Physiol. 72, 517\u2013549 (2010).","journal-title":"Annu. Rev. Physiol."},{"key":"9284_CR13","doi-asserted-by":"publisher","first-page":"39","DOI":"10.3389\/fnut.2020.00039","volume":"7","author":"L Pickel","year":"2020","unstructured":"Pickel, L. & Sung, H.-K. Feeding rhythms and the circadian regulation of metabolism. Front. Nutr. 7, 39 (2020).","journal-title":"Front. Nutr."},{"key":"9284_CR14","doi-asserted-by":"publisher","first-page":"L1056","DOI":"10.1152\/ajplung.00152.2015","volume":"309","author":"IK Sundar","year":"2015","unstructured":"Sundar, I. K., Yao, H., Sellix, M. T. & Rahman, I. Circadian molecular clock in lung pathophysiology. Am. J. Physiol.-Lung Cell. Mol. Physiol. 309, L1056\u2013L1075 (2015).","journal-title":"Am. J. Physiol.-Lung Cell. Mol. Physiol."},{"key":"9284_CR15","doi-asserted-by":"crossref","unstructured":"Bryant, A. J. et al. A wrinkle in time: circadian biology in pulmonary vascular health and disease. Am. J. Physiol. Lung Cell. Mol. Physiol. 322, L84\u2013L101 (2022).","DOI":"10.1152\/ajplung.00037.2021"},{"key":"9284_CR16","doi-asserted-by":"crossref","unstructured":"Parlak, G. C. et al. The secondary pocket of cryptochrome 2 is important for the regulation of its stability and localization. J. Biol. Chem. 298, 102334 (2022).","DOI":"10.1016\/j.jbc.2022.102334"},{"key":"9284_CR17","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2021174118","volume":"118","author":"X Cao","year":"2021","unstructured":"Cao, X., Yang, Y., Selby, C. P., Liu, Z. & Sancar, A. Molecular mechanism of the repressive phase of the mammalian circadian clock. Proc. Natl Acad. Sci. USA 118, e2021174118 (2021).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"9284_CR18","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1096\/fj.13-232629","volume":"28","author":"JW Hwang","year":"2014","unstructured":"Hwang, J. W., Sundar, I. K., Yao, H., Sellix, M. T. & Rahman, I. Circadian clock function is disrupted by environmental tobacco\/cigarette smoke, leading to lung inflammation and injury via a SIRT1-BMAL1 pathway. FASEB J. 28, 176\u2013194 (2014).","journal-title":"FASEB J."},{"key":"9284_CR19","doi-asserted-by":"crossref","unstructured":"Conti, V. et al. Sirtuin 1 and aging theory for chronic obstructive pulmonary disease. Anal. Cell. Pathol. 2015, 897327 (2015).","DOI":"10.1155\/2015\/897327"},{"key":"9284_CR20","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1007\/s12033-007-9013-8","volume":"38","author":"S-Y Ying","year":"2008","unstructured":"Ying, S.-Y., Chang, D. C. & Lin, S.-L. The microRNA (miRNA): overview of the RNA genes that modulate gene function. Mol. Biotechnol. 38, 257\u2013268 (2008).","journal-title":"Mol. Biotechnol."},{"key":"9284_CR21","doi-asserted-by":"publisher","first-page":"112090","DOI":"10.1016\/j.biopha.2021.112090","volume":"142","author":"R Dutta","year":"2021","unstructured":"Dutta, R., Chinnapaiyan, S., Santiago, M., Rahman, I. & Unwalla, H. Gene-specific MicroRNA antagonism protects against HIV Tat and TGF-\u03b2-mediated suppression of CFTR mRNA and function. Biomed. Pharmacother. 142, 112090 (2021).","journal-title":"Biomed. Pharmacother."},{"key":"9284_CR22","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1111\/hiv.12154","volume":"15","author":"T Wang","year":"2014","unstructured":"Wang, T. et al. HIV T at protein affects circadian rhythmicity by interfering with the circadian system. HIV Med. 15, 565\u2013570 (2014).","journal-title":"HIV Med."},{"key":"9284_CR23","first-page":"R1680","volume":"295","author":"MJ Duncan","year":"2008","unstructured":"Duncan, M. J. et al. Effects of chronic expression of the HIV-induced protein, transactivator of transcription, on circadian activity rhythms in mice, with or without morphine. Am. J. Physiol. 295, R1680\u2013R1687 (2008).","journal-title":"Am. J. Physiol."},{"key":"9284_CR24","doi-asserted-by":"publisher","first-page":"e0169161","DOI":"10.1371\/journal.pone.0169161","volume":"12","author":"S Chinnapaiyan","year":"2017","unstructured":"Chinnapaiyan, S. et al. HIV infects bronchial epithelium and suppresses components of the mucociliary clearance apparatus. PLoS ONE 12, e0169161 (2017).","journal-title":"PLoS ONE"},{"key":"9284_CR25","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2020.612360","volume":"10","author":"D Devadoss","year":"2021","unstructured":"Devadoss, D. et al. HIV-1 productively infects and integrates in bronchial epithelial cells. Front. Cell. Infect. Microbiol. 10, 612360 (2021).","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"9284_CR26","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1016\/j.cell.2008.07.010","volume":"134","author":"WJ Belden","year":"2008","unstructured":"Belden, W. J. & Dunlap, J. C. SIRT1 is a circadian deacetylase for core clock components. Cell 134, 212\u2013214 (2008).","journal-title":"Cell"},{"key":"9284_CR27","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1177\/1947601913476948","volume":"4","author":"TF Liu","year":"2013","unstructured":"Liu, T. F. & McCall, C. E. Deacetylation by SIRT1 reprograms inflammation and cancer. Genes Cancer 4, 135\u2013147 (2013).","journal-title":"Genes Cancer"},{"key":"9284_CR28","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1016\/j.chom.2008.02.002","volume":"3","author":"H-S Kwon","year":"2008","unstructured":"Kwon, H.-S. et al. Human immunodeficiency virus type 1 Tat protein inhibits the SIRT1 deacetylase and induces T cell hyperactivation. Cell Host Microbe 3, 158\u2013167 (2008).","journal-title":"Cell Host Microbe"},{"key":"9284_CR29","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.112090","volume":"142","author":"RK Dutta","year":"2021","unstructured":"Dutta, R. K., Chinnapaiyan, S., Santiago, M. J., Rahman, I. & Unwalla, H. J. Gene-specific MicroRNA antagonism protects against HIV Tat and TGF-beta-mediated suppression of CFTR mRNA and function. Biomed. Pharmacother. 142, 112090 (2021).","journal-title":"Biomed. Pharmacother."},{"key":"9284_CR30","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1016\/j.ymthe.2018.11.017","volume":"27","author":"RK Dutta","year":"2019","unstructured":"Dutta, R. K., Chinnapaiyan, S., Rasmussen, L., Raju, S. V. & Unwalla, H. J. A neutralizing aptamer to TGFBR2 and miR-145 antagonism rescue cigarette smoke-and TGF-\u03b2-mediated CFTR expression. Mol. Ther. 27, 442\u2013455 (2019).","journal-title":"Mol. Ther."},{"key":"9284_CR31","first-page":"D148","volume":"48","author":"H-Y Huang","year":"2020","unstructured":"Huang, H.-Y. et al. miRTarBase 2020: updates to the experimentally validated microRNA\u2013target interaction database. Nucleic Acids Res. 48, D148\u2013D154 (2020).","journal-title":"Nucleic Acids Res."},{"key":"9284_CR32","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1016\/j.cell.2008.07.002","volume":"134","author":"Y Nakahata","year":"2008","unstructured":"Nakahata, Y. et al. The NAD+-dependent deacetylase SIRT1 modulates CLOCK-mediated chromatin remodeling and circadian control. Cell 134, 329\u2013340 (2008).","journal-title":"Cell"},{"key":"9284_CR33","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.947067","volume":"13","author":"L Tang","year":"2022","unstructured":"Tang, L. et al. BMAL1\/FOXA2-induced rhythmic fluctuations in IL-6 contribute to nocturnal asthma attacks. Front. Immunol. 13, 947067 (2022).","journal-title":"Front. Immunol."},{"key":"9284_CR34","doi-asserted-by":"publisher","first-page":"E8460","DOI":"10.1073\/pnas.1800431115","volume":"115","author":"JO Early","year":"2018","unstructured":"Early, J. O. et al. Circadian clock protein BMAL1 regulates IL-1\u03b2 in macrophages via NRF2. Proc. Natl Acad. Sci. USA 115, E8460\u2013E8468 (2018).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"9284_CR35","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1165\/rcmb.2013-0538OC","volume":"52","author":"HJ Unwalla","year":"2015","unstructured":"Unwalla, H. J., Ivonnet, P., Dennis, J. S., Conner, G. E. & Salathe, M. Transforming growth factor-beta1 and cigarette smoke inhibit the ability of beta2-agonists to enhance epithelial permeability. Am. J. Respir. Cell Mol. Biol. 52, 65\u201374 (2015).","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"9284_CR36","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11705","volume":"7","author":"T Hamada","year":"2016","unstructured":"Hamada, T. et al. In vivo imaging of clock gene expression in multiple tissues of freely moving mice. Nat. Commun. 7, 11705 (2016).","journal-title":"Nat. Commun."},{"key":"9284_CR37","doi-asserted-by":"crossref","unstructured":"Welsh, D. K., Imaizumi, T. & Kay, S. A. in Methods in Enzymology Vol. 393 269\u2013288 (Elsevier, 2005).","DOI":"10.1016\/S0076-6879(05)93011-5"},{"key":"9284_CR38","doi-asserted-by":"publisher","first-page":"153473541983649","DOI":"10.1177\/1534735419836494","volume":"18","author":"H-H Lin","year":"2019","unstructured":"Lin, H.-H., Qraitem, M., Lian, Y., Taylor, S. R. & Farkas, M. E. Analyses of BMAL1 and PER2 oscillations in a model of breast cancer progression reveal changes with malignancy. Integr. Cancer Ther. 18, 1534735419836494 (2019).","journal-title":"Integr. Cancer Ther."},{"key":"9284_CR39","doi-asserted-by":"crossref","unstructured":"Pervakova, M. Y. et al. High serum level of IL-17 in patients with chronic obstructive pulmonary disease and the alpha-1 antitrypsin PiZ allele. Pulm. Med. 2020, 9738032 (2020).","DOI":"10.1155\/2020\/9738032"},{"key":"9284_CR40","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1164\/ajrccm.163.2.2003122","volume":"163","author":"SD Aaron","year":"2001","unstructured":"Aaron, S. D. et al. Granulocyte inflammatory markers and airway infection during acute exacerbation of chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 163, 349\u2013355 (2001).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"9284_CR41","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s43168-022-00115-z","volume":"16","author":"FG Hussein","year":"2022","unstructured":"Hussein, F. G., Mohammed, R. S., Khattab, R. A. & Al-Sharawy, L. A. Serum interleukin-6 in chronic obstructive pulmonary disease patients and its relation to severity and acute exacerbation.  Egypt. J. Bronchol. 16, 1\u201311 (2022).","journal-title":"Egypt. J. Bronchol."},{"key":"9284_CR42","doi-asserted-by":"publisher","first-page":"223","DOI":"10.3389\/fcell.2020.00223","volume":"8","author":"Y Tan","year":"2020","unstructured":"Tan, Y. et al. FGF2, an immunomodulatory factor in asthma and chronic obstructive pulmonary disease (COPD). Front. Cell Dev. Biol. 8, 223 (2020).","journal-title":"Front. Cell Dev. Biol."},{"key":"9284_CR43","doi-asserted-by":"publisher","first-page":"2070","DOI":"10.1111\/j.1476-5381.2012.01907.x","volume":"166","author":"T Southworth","year":"2012","unstructured":"Southworth, T. et al. IFN-\u03b3 synergistically enhances LPS signalling in alveolar macrophages from COPD patients and controls by corticosteroid-resistant STAT1 activation. Br. J. Pharmacol. 166, 2070\u20132083 (2012).","journal-title":"Br. J. Pharmacol."},{"key":"9284_CR44","doi-asserted-by":"publisher","first-page":"2800","DOI":"10.12659\/MSM.896458","volume":"22","author":"A-X Huang","year":"2016","unstructured":"Huang, A.-X., Lu, L.-W., Liu, W.-J. & Huang, M. Plasma inflammatory cytokine IL-4, IL-8, IL-10, and TNF-\u03b1 levels correlate with pulmonary function in patients with asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome. Med. Sci. Monit. 22, 2800 (2016).","journal-title":"Med. Sci. Monit."},{"key":"9284_CR45","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1080\/07853890.2019.1639809","volume":"51","author":"J Chen","year":"2019","unstructured":"Chen, J. et al. The elevated CXCL5 levels in circulation are associated with lung function decline in COPD patients and cigarette smoking-induced mouse model of COPD. Ann. Med. 51, 314\u2013329 (2019).","journal-title":"Ann. Med."},{"key":"9284_CR46","doi-asserted-by":"publisher","first-page":"1697","DOI":"10.1016\/j.freeradbiomed.2011.07.023","volume":"51","author":"A Cota-Gomez","year":"2011","unstructured":"Cota-Gomez, A., Flores, A. C., Ling, X. F., Varella-Garcia, M. & Flores, S. C. HIV-1 Tat increases oxidant burden in the lungs of transgenic mice. Free Radic. Biol. Med. 51, 1697\u20131707 (2011).","journal-title":"Free Radic. Biol. Med."},{"key":"9284_CR47","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1038\/345084a0","volume":"345","author":"B Ensoli","year":"1990","unstructured":"Ensoli, B., Barillari, G., Salahuddin, S. Z., Gallo, R. C. & Wong-Staal, F. Tat protein of HIV-1 stimulates growth of cells derived from Kaposi\u2019s sarcoma lesions of AIDS patients. Nature 345, 84\u201386 (1990).","journal-title":"Nature"},{"key":"9284_CR48","doi-asserted-by":"publisher","first-page":"1189","DOI":"10.1016\/0092-8674(88)90263-2","volume":"55","author":"AD Frankel","year":"1988","unstructured":"Frankel, A. D. & Pabo, C. O. Cellular uptake of the tat protein from human immunodeficiency virus. Cell 55, 1189\u20131193 (1988).","journal-title":"Cell"},{"key":"9284_CR49","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1128\/jvi.67.1.277-287.1993","volume":"67","author":"B Ensoli","year":"1993","unstructured":"Ensoli, B. et al. Release, uptake, and effects of extracellular human immunodeficiency virus type 1 Tat protein on cell growth and viral transactivation. J. Virol. 67, 277\u2013287 (1993).","journal-title":"J. Virol."},{"key":"9284_CR50","doi-asserted-by":"publisher","first-page":"1421","DOI":"10.1097\/00002030-199712000-00006","volume":"11","author":"HC Chang","year":"1997","unstructured":"Chang, H. C., Samaniego, F., Nair, B. C., Buonaguro, L. & Ensoli, B. HIV-1 Tat protein exits from cells via a leaderless secretory pathway and binds to extracellular matrix-associated heparan sulfate proteoglycans through its basic region. AIDS 11, 1421\u20131431 (1997).","journal-title":"AIDS"},{"key":"9284_CR51","doi-asserted-by":"publisher","first-page":"1326","DOI":"10.1378\/chest.130.5.1326","volume":"130","author":"K Crothers","year":"2006","unstructured":"Crothers, K. et al. Increased COPD among HIV-positive compared to HIV-negative veterans. Chest 130, 1326\u20131333 (2006).","journal-title":"Chest"},{"key":"9284_CR52","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1136\/thorax-2022-218910","volume":"78","author":"RF Thudium","year":"2023","unstructured":"Thudium, R. F. et al. Faster lung function decline in people living with HIV despite adequate treatment: a longitudinal matched cohort study. Thorax 78, 535\u2013542 (2023).","journal-title":"Thorax"},{"key":"9284_CR53","unstructured":"Life Span as a Biomarker. The Jackson laboratory https:\/\/www.jax.org\/research-and-faculty\/research-labs\/the-harrison-lab\/gerontology\/life-span-as-a-biomarker."},{"key":"9284_CR54","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1038\/nm.3599","volume":"20","author":"J Gibbs","year":"2014","unstructured":"Gibbs, J. et al. An epithelial circadian clock controls pulmonary inflammation and glucocorticoid action. Nat. Med. 20, 919\u2013926 (2014).","journal-title":"Nat. Med."},{"key":"9284_CR55","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1152\/japplphysiol.00244.2012","volume":"113","author":"H Hadden","year":"2012","unstructured":"Hadden, H., Soldin, S. J. & Massaro, D. Circadian disruption alters mouse lung clock gene expression and lung mechanics. J. Appl. Physiol. 113, 385\u2013392 (2012).","journal-title":"J. Appl. Physiol."},{"key":"9284_CR56","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1136\/thx.2003.019588","volume":"59","author":"WQ Gan","year":"2004","unstructured":"Gan, W. Q., Man, S., Senthilselvan, A. & Sin, D. Association between chronic obstructive pulmonary disease and systemic inflammation: a systematic review and a meta-analysis. Thorax 59, 574\u2013580 (2004).","journal-title":"Thorax"},{"key":"9284_CR57","doi-asserted-by":"publisher","first-page":"S72","DOI":"10.1016\/j.jana.2012.10.006","volume":"24","author":"DM Taibi","year":"2013","unstructured":"Taibi, D. M. Sleep disturbances in persons living with HIV. J. Assoc. Nurses AIDS Care 24, S72\u2013S85 (2013).","journal-title":"J. Assoc. Nurses AIDS Care"},{"key":"9284_CR58","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1016\/j.cell.2008.06.050","volume":"134","author":"G Asher","year":"2008","unstructured":"Asher, G. et al. SIRT1 regulates circadian clock gene expression through PER2 deacetylation. Cell 134, 317\u2013328 (2008).","journal-title":"Cell"},{"key":"9284_CR59","doi-asserted-by":"publisher","DOI":"10.1038\/srep28633","volume":"6","author":"R-H Wang","year":"2016","unstructured":"Wang, R.-H. et al. Negative reciprocal regulation between Sirt1 and Per2 modulates the circadian clock and aging. Sci. Rep. 6, 28633 (2016).","journal-title":"Sci. Rep."},{"key":"9284_CR60","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/j.bbrc.2012.06.084","volume":"424","author":"BK Thakur","year":"2012","unstructured":"Thakur, B. K., Chandra, A., Dittrich, T., Welte, K. & Chandra, P. Inhibition of SIRT1 by HIV-1 viral protein Tat results in activation of p53 pathway. Biochem. Biophys. Res. Commun. 424, 245\u2013250 (2012).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"9284_CR61","doi-asserted-by":"publisher","first-page":"2009","DOI":"10.3390\/cells13232009","volume":"13","author":"K Panda","year":"2024","unstructured":"Panda, K. et al. HIV-1 tat protein and cigarette smoke mediated ADAM17 upregulation can lead to impaired mucociliary clearance. Cells 13, 2009 (2024).","journal-title":"Cells"},{"key":"9284_CR62","doi-asserted-by":"publisher","first-page":"E2457","DOI":"10.1073\/pnas.1206274109","volume":"109","author":"ML Spengler","year":"2012","unstructured":"Spengler, M. L. et al. Core circadian protein CLOCK is a positive regulator of NF-kappaB-mediated transcription. Proc. Natl Acad. Sci. USA 109, E2457\u2013E2465 (2012).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"9284_CR63","doi-asserted-by":"publisher","first-page":"e46364","DOI":"10.1371\/journal.pone.0046364","volume":"7","author":"H Yang","year":"2012","unstructured":"Yang, H. et al. SIRT1 activators suppress inflammatory responses through promotion of p65 deacetylation and inhibition of NF-kappaB activity. PLoS ONE 7, e46364 (2012).","journal-title":"PLoS ONE"},{"key":"9284_CR64","doi-asserted-by":"crossref","unstructured":"Di Stefano, A. et al. Blood MCP-1 levels are increased in chronic obstructive pulmonary disease patients with prevalent emphysema. Int. J. Chron. Obstruct. Pulmon. Dis. 13, 1691\u20131700 (2018).","DOI":"10.2147\/COPD.S159915"},{"key":"9284_CR65","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1165\/rcmb.2019-0297OC","volume":"62","author":"J Yang","year":"2020","unstructured":"Yang, J. et al. Diverse injury pathways induce alveolar epithelial cell CCL2\/12, which promotes lung fibrosis. Am. J. Respir. Cell Mol. Biol. 62, 622\u2013632 (2020).","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"9284_CR66","doi-asserted-by":"publisher","first-page":"2711","DOI":"10.4049\/jimmunol.1100479","volume":"187","author":"M Li","year":"2011","unstructured":"Li, M. et al. Emergence of fibroblasts with a proinflammatory epigenetically altered phenotype in severe hypoxic pulmonary hypertension.  J. Immunol. 187, 2711\u20132722 (2011).","journal-title":"J. Immunol."},{"key":"9284_CR67","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1007\/s11914-019-00545-7","volume":"17","author":"BS Mulholland","year":"2019","unstructured":"Mulholland, B. S., Forwood, M. R. & Morrison, N. A. Monocyte chemoattractant protein-1 (MCP-1\/CCL2) drives activation of bone remodelling and skeletal metastasis. Curr. Osteoporos. Rep. 17, 538\u2013547 (2019).","journal-title":"Curr. Osteoporos. Rep."},{"key":"9284_CR68","doi-asserted-by":"publisher","first-page":"1429213","DOI":"10.1155\/2022\/1429213","volume":"2022","author":"W Xue","year":"2022","unstructured":"Xue, W., Ma, J., Li, Y. & Xie, C. Role of CD4+ T and CD8+ T lymphocytes-mediated cellular immunity in pathogenesis of chronic obstructive pulmonary disease. J. Immunol. Res. 2022, 1429213 (2022).","journal-title":"J. Immunol. Res."},{"key":"9284_CR69","doi-asserted-by":"publisher","first-page":"1045","DOI":"10.2147\/COPD.S155306","volume":"14","author":"DK Narendra","year":"2019","unstructured":"Narendra, D. K. & Hanania, N. A. Targeting IL-5 in COPD. Int. J. Chron. Obstr. Pulm. Dis. 14, 1045\u20131051 (2019).","journal-title":"Int. J. Chron. Obstr. Pulm. Dis."},{"key":"9284_CR70","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1172\/JCI5909","volume":"103","author":"Z Zhu","year":"1999","unstructured":"Zhu, Z. et al. Pulmonary expression of interleukin-13 causes inflammation, mucus hypersecretion, subepithelial fibrosis, physiologic abnormalities, and eotaxin production.  J. Clin. Investig. 103, 779\u2013788 (1999).","journal-title":"J. Clin. Investig."},{"key":"9284_CR71","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1038\/s41590-018-0276-y","volume":"20","author":"D Aran","year":"2019","unstructured":"Aran, D. et al. Reference-based analysis of lung single-cell sequencing reveals a transitional profibrotic macrophage. Nat. Immunol. 20, 163\u2013172 (2019).","journal-title":"Nat. Immunol."},{"key":"9284_CR72","doi-asserted-by":"publisher","first-page":"2831","DOI":"10.1097\/JS9.0000000000000103","volume":"109","author":"M Shafaati","year":"2023","unstructured":"Shafaati, M. et al. The relevance of the circadian timing system role in patients with HIV\/AIDS: a quick glance. Int. J. Surg. 109, 2831\u20132834 (2023).","journal-title":"Int. J. Surg."},{"key":"9284_CR73","doi-asserted-by":"publisher","first-page":"584637","DOI":"10.3389\/fphar.2020.584637","volume":"11","author":"KP Maremanda","year":"2020","unstructured":"Maremanda, K. P., Sundar, I. K., Li, D. & Rahman, I. Age-dependent assessment of genes involved in cellular senescence, telomere, and mitochondrial pathways in human lung tissue of smokers, COPD, and IPF: associations with SARS-CoV-2 COVID-19 ACE2-TMPRSS2-Furin-DPP4 axis. Front. Pharmacol. 11, 584637 (2020).","journal-title":"Front. Pharmacol."},{"key":"9284_CR74","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13148-017-0335-5","volume":"9","author":"IK Sundar","year":"2017","unstructured":"Sundar, I. K. et al. DNA methylation profiling in peripheral lung tissues of smokers and patients with COPD. Clin. Epigenetics 9, 1\u201318 (2017).","journal-title":"Clin. Epigenetics"},{"key":"9284_CR75","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-49056-6","volume":"9","author":"S Chinnapaiyan","year":"2019","unstructured":"Chinnapaiyan, S. et al. TGF-\u03b21 increases viral burden and promotes HIV-1 latency in primary differentiated human bronchial epithelial cells. Sci. Rep. 9, 12552 (2019).","journal-title":"Sci. Rep."},{"key":"9284_CR76","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-26095-z","volume":"8","author":"S Chinnapaiyan","year":"2018","unstructured":"Chinnapaiyan, S. et al. Cigarette smoke promotes HIV infection of primary bronchial epithelium and additively suppresses CFTR function. Sci. Rep. 8, 7984 (2018).","journal-title":"Sci. Rep."},{"key":"9284_CR77","doi-asserted-by":"crossref","unstructured":"Ramsey, K.M. et al. Circadian measurements of sirtuin biology. Methods Mol Biol. Vol. 1077, 285-302 (Springer, 2013).","DOI":"10.1007\/978-1-62703-637-5_19"},{"key":"9284_CR78","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.70199","volume":"13","author":"MI Faizan","year":"2025","unstructured":"Faizan, M. I. et al. Genetic diversity leads to differential inflammatory responses to cigarette smoke in mice. Physiol. Rep. 13, e70199 (2025).","journal-title":"Physiol. Rep."},{"key":"9284_CR79","doi-asserted-by":"publisher","first-page":"2032","DOI":"10.1172\/JCI60132","volume":"122","author":"H Yao","year":"2012","unstructured":"Yao, H. et al. SIRT1 protects against emphysema via FOXO3-mediated reduction of premature senescence in mice.  J. Clin. Investig. 122, 2032\u20132045 (2012).","journal-title":"J. Clin. Investig."},{"key":"9284_CR80","doi-asserted-by":"publisher","first-page":"15571","DOI":"10.1073\/pnas.1007625107","volume":"107","author":"H Yao","year":"2010","unstructured":"Yao, H. et al. Extracellular superoxide dismutase protects against pulmonary emphysema by attenuating oxidative fragmentation of ECM. Proc. Natl Acad. Sci. USA 107, 15571\u201315576 (2010).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"9284_CR81","doi-asserted-by":"publisher","first-page":"1289","DOI":"10.1038\/s41592-019-0619-0","volume":"16","author":"I Korsunsky","year":"2019","unstructured":"Korsunsky, I. et al. Fast, sensitive and accurate integration of single-cell data with Harmony. Nat. Methods 16, 1289\u20131296 (2019).","journal-title":"Nat. Methods"},{"key":"9284_CR82","doi-asserted-by":"publisher","first-page":"3573","DOI":"10.1016\/j.cell.2021.04.048","volume":"184","author":"Y Hao","year":"2021","unstructured":"Hao, Y. et al. Integrated analysis of multimodal single-cell data. Cell 184, 3573\u20133587.e3529 (2021).","journal-title":"Cell"},{"key":"9284_CR83","doi-asserted-by":"publisher","first-page":"1888","DOI":"10.1016\/j.cell.2019.05.031","volume":"177","author":"T Stuart","year":"2019","unstructured":"Stuart, T. et al. Comprehensive integration of single-cell data. Cell 177, 1888\u20131902.e1821 (2019).","journal-title":"Cell"},{"key":"9284_CR84","doi-asserted-by":"publisher","first-page":"1563","DOI":"10.1038\/s41591-023-02327-2","volume":"29","author":"L Sikkema","year":"2023","unstructured":"Sikkema, L. et al. An integrated cell atlas of the lung in health and disease. Nat. Med. 29, 1563\u20131577 (2023).","journal-title":"Nat. Med."},{"key":"9284_CR85","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-25960-2","volume":"12","author":"JW Squair","year":"2021","unstructured":"Squair, J. W. et al. Confronting false discoveries in single-cell differential expression. Nat. Commun. 12, 5692 (2021).","journal-title":"Nat. Commun."}],"container-title":["Communications Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-09284-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-09284-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-09284-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T03:02:10Z","timestamp":1767582130000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-09284-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,5]]},"references-count":85,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["9284"],"URL":"https:\/\/doi.org\/10.1038\/s42003-025-09284-1","relation":{},"ISSN":["2399-3642"],"issn-type":[{"value":"2399-3642","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,5]]},"assertion":[{"value":"8 April 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 November 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 January 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"11"}}