{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T09:30:37Z","timestamp":1784799037839,"version":"3.55.0"},"reference-count":123,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,5,23]],"date-time":"2023-05-23T00:00:00Z","timestamp":1684800000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["R01 HL158316"],"award-info":[{"award-number":["R01 HL158316"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>People living with HIV (PLWH) have an elevated risk of chronic obstructive pulmonary disease (COPD) and are at a higher risk of asthma and worse outcomes. Even though the combination of antiretroviral therapy (cART) has significantly improved the life expectancy of HIV-infected patients, it still shows a higher incidence of COPD in patients as young as 40 years old. Circadian rhythms are endogenous 24 h oscillations that regulate physiological processes, including immune responses. Additionally, they play a significant role in health and diseases by regulating viral replication and its corresponding immune responses. Circadian genes play an essential role in lung pathology, especially in PLWH. The dysregulation of core clock and clock output genes plays an important role in chronic inflammation and aberrant peripheral circadian rhythmicity, particularly in PLWH. In this review, we explained the mechanism underlying circadian clock dysregulation in HIV and its effects on the development and progression of COPD. Furthermore, we discussed potential therapeutic approaches to reset the peripheral molecular clocks and mitigate airway inflammation.<\/jats:p>","DOI":"10.3390\/ijms24119140","type":"journal-article","created":{"date-parts":[[2023,5,23]],"date-time":"2023-05-23T08:14:28Z","timestamp":1684829668000},"page":"9140","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Circadian-Coupled Genes Expression and Regulation in HIV-Associated Chronic Obstructive Pulmonary Disease (COPD) and Lung Comorbidities"],"prefix":"10.3390","volume":"24","author":[{"given":"Kingshuk","family":"Panda","sequence":"first","affiliation":[{"name":"Department of Immunology and Nanomedicine, Herbert Wertheim College of Medicine, Florida International University, 11200 SW 8th Street, Miami, FL 33199, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5633-9749","authenticated-orcid":false,"given":"Srinivasan","family":"Chinnapaiyan","sequence":"additional","affiliation":[{"name":"Department of Immunology and Nanomedicine, Herbert Wertheim College of Medicine, Florida International University, 11200 SW 8th Street, Miami, FL 33199, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md. Sohanur","family":"Rahman","sequence":"additional","affiliation":[{"name":"Department of Immunology and Nanomedicine, Herbert Wertheim College of Medicine, Florida International University, 11200 SW 8th Street, Miami, FL 33199, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria J.","family":"Santiago","sequence":"additional","affiliation":[{"name":"Department of Immunology and Nanomedicine, Herbert Wertheim College of Medicine, Florida International University, 11200 SW 8th Street, Miami, FL 33199, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen M.","family":"Black","sequence":"additional","affiliation":[{"name":"Department of Cellular Biology & Pharmacology, Herbert Wertheim College of Medicine, Florida International University, 11200 SW 8th Street, Miami, FL 33199, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hoshang J.","family":"Unwalla","sequence":"additional","affiliation":[{"name":"Department of Immunology and Nanomedicine, Herbert Wertheim College of Medicine, Florida International University, 11200 SW 8th Street, Miami, FL 33199, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1080\/09540121.2022.2076801","article-title":"Chronic pain and substance use disorders among older sexual minority men living with HIV: Implications for HIV disease management across the HIV care continuum","volume":"35","author":"Taylor","year":"2022","journal-title":"AIDS Care"},{"key":"ref_2","unstructured":"CDC (2023, April 23). Undertanding the HIV Care Continuum, Available online: https:\/\/www.cdc.gov\/hiv\/pdf\/library\/factsheets\/cdc-hiv-care-continuum.pdf."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e193","DOI":"10.1016\/S2214-109X(17)30451-5","article-title":"Prevalence of chronic obstructive pulmonary disease in the global population with HIV: A systematic review and meta-analysis","volume":"6","author":"Bigna","year":"2018","journal-title":"Lancet Glob. Health"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1513\/pats.201006-045WR","article-title":"HIV and chronic obstructive pulmonary disease: Is it worse and why?","volume":"8","author":"Morris","year":"2011","journal-title":"Proc. Am. Thorac. Soc."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1097\/QAI.0000000000000552","article-title":"HIV infection is associated with increased risk for acute exacerbation of COPD","volume":"69","author":"Lambert","year":"2015","journal-title":"JAIDS J. Acquir. Immune Defic. Syndr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s41606-017-0019-2","article-title":"A circadian based inflammatory response\u2013implications for respiratory disease and treatment","volume":"1","author":"Comas","year":"2017","journal-title":"Sleep Sci. Pract."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e12904","DOI":"10.1111\/pim.12904","article-title":"Circadian rhythms in immunity and host-parasite interactions","volume":"44","author":"Hunter","year":"2022","journal-title":"Parasite Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"L1056","DOI":"10.1152\/ajplung.00152.2015","article-title":"Circadian molecular clock in lung pathophysiology","volume":"309","author":"Sundar","year":"2015","journal-title":"Am. J. Physiol.-Lung Cell. Mol. Physiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1111\/hiv.12154","article-title":"HIV T at protein affects circadian rhythmicity by interfering with the circadian system","volume":"15","author":"Wang","year":"2014","journal-title":"HIV Med."},{"key":"ref_10","first-page":"437","article-title":"Circadian rhythm alteration in HIV infected subjects","volume":"341","author":"Swoyer","year":"1990","journal-title":"Prog. Clin. Biol. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"R1680","DOI":"10.1152\/ajpregu.90496.2008","article-title":"Effects of chronic expression of the HIV-induced protein, transactivator of transcription, on circadian activity rhythms in mice, with or without morphine","volume":"295","author":"Duncan","year":"2008","journal-title":"Am. J. Physiol.-Regul. Integr. Comp. Physiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1177\/07487304221131114","article-title":"Chronotype in patients with immune-mediated inflammatory disease: A systematic review","volume":"38","author":"Butler","year":"2023","journal-title":"J. Biol. Rhythm."},{"key":"ref_13","unstructured":"Rijo-Ferreira, F., and Takahashi, J.S. (2022). Seminars in Cell & Developmental Biology, Elsevier."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.cell.2008.07.010","article-title":"SIRT1 is a circadian deacetylase for core clock components","volume":"134","author":"Belden","year":"2008","journal-title":"Cell"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"R656","DOI":"10.1152\/ajpregu.00179.2005","article-title":"HIV protein, transactivator of transcription, alters circadian rhythms through the light entrainment pathway","volume":"289","author":"Clark","year":"2005","journal-title":"Am. J. Physiol.-Regul. Integr. Comp. Physiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2119","DOI":"10.1097\/QAD.0000000000001937","article-title":"Variation in cell associated unspliced HIV RNA on antiretroviral therapy is associated with the circadian regulator BMAL-1","volume":"32","author":"Chang","year":"2018","journal-title":"AIDS"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1159\/000502261","article-title":"Immune-modulation in chronic obstructive pulmonary disease: Current concepts and future strategies","volume":"99","author":"Hogg","year":"2020","journal-title":"Respiration"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"S169","DOI":"10.1513\/AnnalsATS.201503-126AW","article-title":"Immune dysfunction in patients with chronic obstructive pulmonary disease","volume":"12","author":"Bhat","year":"2015","journal-title":"Ann. Am. Thorac. Soc."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1085551","DOI":"10.3389\/fimmu.2022.1085551","article-title":"Airway microbiome-immune crosstalk in chronic obstructive pulmonary disease","volume":"13","author":"Kayongo","year":"2023","journal-title":"Front. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1152\/physrev.00039.2018","article-title":"Pathogenesis of HIV-related lung disease: Immunity, infection, and inflammation","volume":"100","author":"Cribbs","year":"2020","journal-title":"Physiol. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5637","DOI":"10.3389\/fimmu.2021.808722","article-title":"Pulmonary immune dysregulation and viral persistence during HIV infection","volume":"12","author":"Alexandrova","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Chinnapaiyan, S., Parira, T., Dutta, R., Agudelo, M., Morris, A., Nair, M., and Unwalla, H. (2017). HIV infects bronchial epithelium and suppresses components of the mucociliary clearance apparatus. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0169161"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.amjms.2020.07.026","article-title":"HIV impairs alveolar macrophage function via MicroRNA-144-induced suppression of Nrf2","volume":"361","author":"Fan","year":"2021","journal-title":"Am. J. Med. Sci."},{"key":"ref_24","unstructured":"Charles, T.P., and Shellito, J.E. (2016). Seminars in Respiratory and Critical Care Medicine, Thieme Medical Publishers."},{"key":"ref_25","first-page":"E83","article-title":"Incidence of chronic obstructive pulmonary disease in people with HIV in Ontario, 1996\u20132015: A retrospective population-based cohort study","volume":"8","author":"Antoniou","year":"2020","journal-title":"Can. Med. Assoc. Open Access J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1513\/pats.201009-058WR","article-title":"Cigarette smoking in the HIV-infected population","volume":"8","author":"Rahmanian","year":"2011","journal-title":"Proc. Am. Thorac. Soc."},{"key":"ref_27","first-page":"S106","article-title":"Trachebronchial Mucociliary Dysfunction in HIV","volume":"10","author":"Unwalla","year":"2015","journal-title":"J. Neuroimmune Pharm."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1896","DOI":"10.2105\/AJPH.2009.188664","article-title":"Smoking-related health risks among persons with HIV in the Strategies for Management of Antiretroviral Therapy clinical trial","volume":"100","author":"Lifson","year":"2010","journal-title":"Am. J. Public Health"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1164\/rccm.200912-1858OC","article-title":"Pulmonary function abnormalities in HIV-infected patients during the current antiretroviral therapy era","volume":"182","author":"Gingo","year":"2010","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_30","first-page":"1","article-title":"Predictors of impaired pulmonary function in people living with HIV in an urban African setting","volume":"22","author":"Barth","year":"2021","journal-title":"South. Afr. J. HIV Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e27124","DOI":"10.1097\/MD.0000000000027124","article-title":"A cross-sectional analysis of diagnosis and management of chronic obstructive pulmonary disease in people living with HIV: Opportunities for improvement","volume":"100","author":"Zifodya","year":"2021","journal-title":"Medicine"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1097\/COH.0000000000000679","article-title":"Recent advances in HIV-associated chronic lung disease clinical research","volume":"16","author":"Kunisaki","year":"2021","journal-title":"Curr. Opin. HIV AIDS"},{"key":"ref_33","unstructured":"Modi, P., and Cascella, M. (2020). Diffusing Capacity of the Lungs for Carbon Monoxide, StatPearls Publishing."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1111\/hiv.12785","article-title":"Significant chronic airway abnormalities in never-smoking HIV-infected patients","volume":"20","author":"Besutti","year":"2019","journal-title":"HIV Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1850","DOI":"10.1093\/cid\/civ687","article-title":"Changing trends in complications and mortality rates among US youth and young adults with HIV infection in the era of combination antiretroviral therapy","volume":"61","author":"Mirani","year":"2015","journal-title":"Clin. Infect. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1186\/s12931-018-0898-5","article-title":"The impact of HIV on the prevalence of asthma in Uganda: A general population survey","volume":"19","author":"Kirenga","year":"2018","journal-title":"Respir. Res."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Barton, J.H., Ireland, A., Fitzpatrick, M., Kessinger, C., Camp, D., Weinman, R., McMahon, D., Leader, J.K., Holguin, F., and Wenzel, S.E. (2016). Adiposity influences airway wall thickness and the asthma phenotype of HIV-associated obstructive lung disease: A cross-sectional study. BMC Pulm. Med., 16.","DOI":"10.1186\/s12890-016-0274-5"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e000472","DOI":"10.1136\/bmjresp-2019-000472","article-title":"Influence of HIV status on the management of acute asthma exacerbations","volume":"6","author":"Adrish","year":"2019","journal-title":"BMJ Open Respir. Res."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Kendall, C.E., Wong, J., Taljaard, M., Glazier, R.H., Hogg, W., Younger, J., and Manuel, D.G. (2014). A cross-sectional, population-based study measuring comorbidity among people living with HIV in Ontario. BMC Public Health, 14.","DOI":"10.1186\/1471-2458-14-161"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1016\/j.jaci.2011.11.015","article-title":"Asthma diagnosis and airway bronchodilator response in HIV-infected patients","volume":"129","author":"Gingo","year":"2012","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"154874","DOI":"10.1016\/j.cyto.2019.154874","article-title":"The elevated systemic cytokine levels in HIV patients are not associated with an elevated pulmonary cytokine environment","volume":"126","author":"Vega","year":"2020","journal-title":"Cytokine"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1164\/ajrccm.164.4.2010019","article-title":"Prevalence of bronchial hyperresponsiveness among HIV-infected men","volume":"164","author":"Poirier","year":"2001","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1093\/jnen\/64.6.498","article-title":"HIV-1 gp120 proteins alter tight junction protein expression and brain endothelial cell permeability: Implications for the pathogenesis of HIV-associated dementia","volume":"64","author":"Kanmogne","year":"2005","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1023\/A:1023892223074","article-title":"HIV-1 Tat protein and endothelium: From protein\/cell interaction to AIDS-associated pathologies","volume":"5","author":"Rusnati","year":"2002","journal-title":"Angiogenesis"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"L729","DOI":"10.1152\/ajplung.00087.2009","article-title":"Golgi dysfunction is a common feature in idiopathic human pulmonary hypertension and vascular lesions in SHIV-nef-infected macaques","volume":"297","author":"Sehgal","year":"2009","journal-title":"Am. J. Physiol.-Lung Cell. Mol. Physiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1093\/jnci\/djr076","article-title":"Cancer burden in the HIV-infected population in the United States","volume":"103","author":"Shiels","year":"2011","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"507","DOI":"10.7326\/M14-2768","article-title":"Cumulative incidence of cancer among persons with HIV in North America: A cohort study","volume":"163","author":"Silverberg","year":"2015","journal-title":"Ann. Intern. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2109","DOI":"10.1097\/QAD.0000000000000382","article-title":"Writing Committee of the Cancer Risk Group of the French Hospital Database on HIV. Risk of non-AIDS-defining cancers among HIV-1-infected individuals in France between 1997 and 2009: Results from a French cohort","volume":"28","author":"Hleyhel","year":"2014","journal-title":"Aids"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/0002-9343(85)90080-4","article-title":"Circadian variation in airway function","volume":"79","author":"Barnes","year":"1985","journal-title":"Am. J. Med."},{"key":"ref_50","first-page":"S167","article-title":"Airway inflammation in chronic obstructive pulmonary disease","volume":"6","author":"Angelis","year":"2014","journal-title":"J. Thorac. Dis."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"9927","DOI":"10.1038\/srep09927","article-title":"Influenza A virus-dependent remodeling of pulmonary clock function in a mouse model of COPD","volume":"5","author":"Sundar","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/mi.2017.24","article-title":"BMAL1 links the circadian clock to viral airway pathology and asthma phenotypes","volume":"11","author":"Ehlers","year":"2018","journal-title":"Mucosal Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Hastings, M.H., Maywood, E.S., and Brancaccio, M. (2019). The mammalian circadian timing system and the suprachiasmatic nucleus as its pacemaker. Biology, 8.","DOI":"10.3390\/biology8010013"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1038\/nrg.2016.150","article-title":"Transcriptional architecture of the mammalian circadian clock","volume":"18","author":"Takahashi","year":"2017","journal-title":"Nat. Rev. Genet."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"32064","DOI":"10.1074\/jbc.M114.578278","article-title":"The mammalian circadian clock protein period counteracts cryptochrome in phosphorylation dynamics of circadian locomotor output cycles kaput (CLOCK)","volume":"289","author":"Matsumura","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"27971","DOI":"10.1073\/pnas.1920653117","article-title":"The human CRY1 tail controls circadian timing by regulating its association with CLOCK: BMAL1","volume":"117","author":"Parico","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Mavroudis, P.D., DuBois, D.C., Almon, R.R., and Jusko, W.J. (2018). Modeling circadian variability of core-clock and clock-controlled genes in four tissues of the rat. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0197534"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1164\/rccm.200708-1269OC","article-title":"SIRT1, an antiinflammatory and antiaging protein, is decreased in lungs of patients with chronic obstructive pulmonary disease","volume":"177","author":"Rajendrasozhan","year":"2008","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1096\/fj.13-232629","article-title":"Circadian clock function is disrupted by environmental tobacco\/cigarette smoke, leading to lung inflammation and injury via a SIRT1-BMAL1 pathway","volume":"28","author":"Hwang","year":"2014","journal-title":"FASEB J."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Li, L., Zhang, M., Zhao, C., Cheng, Y., Liu, C., and Shi, M. (2022). Circadian clock gene Clock-Bmal1 regulates cellular senescence in Chronic obstructive pulmonary disease. BMC Pulm. Med., 22.","DOI":"10.1186\/s12890-022-02237-y"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"e13440","DOI":"10.14814\/phy2.13440","article-title":"Exposure to electronic cigarette vapors affects pulmonary and systemic expression of circadian molecular clock genes","volume":"5","author":"Lechasseur","year":"2017","journal-title":"Physiol. Rep."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1126\/science.8171325","article-title":"Mutagenesis and mapping of a mouse gene, Clock, essential for circadian behavior","volume":"264","author":"Vitaterna","year":"1994","journal-title":"Science"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/j.celrep.2018.06.026","article-title":"The circadian clock controls immune checkpoint pathway in sepsis","volume":"24","author":"Deng","year":"2018","journal-title":"Cell Rep."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.immuni.2011.12.017","article-title":"The circadian clock controls toll-like receptor 9-mediated innate and adaptive immunity","volume":"36","author":"Silver","year":"2012","journal-title":"Immunity"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1126\/science.1240636","article-title":"Circadian gene Bmal1 regulates diurnal oscillations of Ly6Chi inflammatory monocytes","volume":"341","author":"Nguyen","year":"2013","journal-title":"Science"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1073\/pnas.1106750109","article-title":"The nuclear receptor REV-ERB\u03b1 mediates circadian regulation of innate immunity through selective regulation of inflammatory cytokines","volume":"109","author":"Gibbs","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1089\/ars.2013.5539","article-title":"Oxidative stress and inflammation modulate Rev-erb\u03b1 signaling in the neonatal lung and affect circadian rhythmicity","volume":"21","author":"Yang","year":"2014","journal-title":"Antioxid. Redox Signal."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"5102","DOI":"10.1073\/pnas.1812405116","article-title":"Circadian clock protein Rev-erb\u03b1 regulates neuroinflammation","volume":"116","author":"Griffin","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"371","DOI":"10.2147\/JAA.S302508","article-title":"Disrupted expression of circadian clock genes in patients with bronchial asthma","volume":"14","author":"Chen","year":"2021","journal-title":"J. Asthma Allergy"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1097\/COH.0b013e32835fc68a","article-title":"Overcoming pharmacologic sanctuaries","volume":"8","author":"Cory","year":"2013","journal-title":"Curr. Opin. HIV AIDS"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1111\/j.1365-2796.2011.02457.x","article-title":"HIV reservoirs and the possibility of a cure for HIV infection","volume":"270","author":"Palmer","year":"2011","journal-title":"J. Intern. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1038\/nm.2111","article-title":"HIV-1 replication and immune dynamics are affected by raltegravir intensification of HAART-suppressed subjects","volume":"16","author":"Buzon","year":"2010","journal-title":"Nat. Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.1093\/infdis\/jit453","article-title":"Increase in 2-long terminal repeat circles and decrease in D-dimer after raltegravir intensification in patients with treated HIV infection: A randomized, placebo-controlled trial","volume":"208","author":"Hatano","year":"2013","journal-title":"J. Infect. Dis."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1164\/ajrccm.159.5.9808031","article-title":"Lymphocytic alveolitis, bronchoalveolar lavage viral load, and outcome in human immunodeficiency virus infection","volume":"159","author":"Twigg","year":"1999","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1007\/BF03401889","article-title":"Low copy number and limited variability of proviral DNA in alveolar macrophages from HIV-1-infected patients: Evidence for genetic differences in HIV-1 between lung and blood macrophage populations","volume":"1","author":"Nakata","year":"1995","journal-title":"Mol. Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1164\/ajrccm\/143.4_Pt_1.850","article-title":"Frequent identification of HIV-1 DNA in bronchoalveolar lavage cells obtained from individuals with the acquired immunodeficiency syndrome","volume":"143","author":"Rose","year":"1991","journal-title":"Am. Rev. Respir. Dis."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Devadoss, D., Singh, S.P., Acharya, A., Do, K.C., Periyasamy, P., Manevski, M., Mishra, N., Tellez, C., Ramakrishnan, S., and Belinsky, S. (2020). Lung Bronchial Epithelial Cells are HIV Targets for Proviral Genomic Integration. bioRxiv, bioRxiv:2020.06.01.126821.","DOI":"10.1101\/2020.06.01.126821"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"5428","DOI":"10.1172\/JCI121935","article-title":"Cigarette smoke and HIV synergistically affect lung pathology in cynomolgus macaques","volume":"128","author":"Chand","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"12552","DOI":"10.1038\/s41598-019-49056-6","article-title":"TGF-beta1 increases viral burden and promotes HIV-1 latency in primary differentiated human bronchial epithelial cells","volume":"9","author":"Chinnapaiyan","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"7984","DOI":"10.1038\/s41598-018-26095-z","article-title":"Cigarette smoke promotes HIV infection of primary bronchial epithelium and additively suppresses CFTR function","volume":"8","author":"Chinnapaiyan","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.cell.2021.12.038","article-title":"The loud minority: Transcriptionally active HIV-1-infected cells survive, proliferate, and persist","volume":"185","author":"Collora","year":"2022","journal-title":"Cell"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.cell.2021.12.011","article-title":"Parallel analysis of transcription, integration, and sequence of single HIV-1 proviruses","volume":"185","author":"Einkauf","year":"2022","journal-title":"Cell"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1093\/infdis\/165.1.185","article-title":"Abnormalities of morning serum cortisol levels and circadian rhythms of CD4+ lymphocyte counts in human immunodeficiency virus type 1-infected adult patients","volume":"165","author":"Malone","year":"1992","journal-title":"J. Infect. Dis."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.3109\/07420528.2015.1087021","article-title":"Circadian regulation gene polymorphisms are associated with sleep disruption and duration, and circadian phase and rhythm in adults with HIV","volume":"32","author":"Lee","year":"2015","journal-title":"Chronobiol. Int."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.chom.2008.02.002","article-title":"Human immunodeficiency virus type 1 Tat protein inhibits the SIRT1 deacetylase and induces T cell hyperactivation","volume":"3","author":"Kwon","year":"2008","journal-title":"Cell Host Microbe"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"362","DOI":"10.3389\/fcimb.2020.00362","article-title":"Per2 upregulation in circulating hematopoietic progenitor cells during chronic hiv infection","volume":"10","author":"Bordoni","year":"2020","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"402","DOI":"10.3389\/fendo.2018.00402","article-title":"Overview of microRNA biogenesis, mechanisms of actions, and circulation","volume":"9","author":"Hayder","year":"2018","journal-title":"Front. Endocrinol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.omtn.2019.09.007","article-title":"Aberrant microRNAomics in pulmonary complications: Implications in lung health and diseases","volume":"18","author":"Dutta","year":"2019","journal-title":"Mol. Ther.-Nucleic Acids"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"D155","DOI":"10.1093\/nar\/gky1141","article-title":"miRBase: From microRNA sequences to function","volume":"47","author":"Kozomara","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.cell.2004.12.035","article-title":"Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets","volume":"120","author":"Lewis","year":"2005","journal-title":"Cell"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1038\/nrm2632","article-title":"Biogenesis of small RNAs in animals","volume":"10","author":"Kim","year":"2009","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"D140","DOI":"10.1093\/nar\/gkj112","article-title":"miRBase: microRNA sequences, targets and gene nomenclature","volume":"34","author":"Grocock","year":"2006","journal-title":"Nucleic Acids Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1038\/nature03315","article-title":"Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs","volume":"433","author":"Lim","year":"2005","journal-title":"Nature"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.ejphar.2016.09.015","article-title":"The roles of miRNAs as potential biomarkers in lung diseases","volume":"791","author":"Alipoor","year":"2016","journal-title":"Eur. J. Pharmacol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"3185","DOI":"10.3389\/fmicb.2018.03185","article-title":"Potential application of microRNA profiling to the diagnosis and prognosis of HIV-1 infection","volume":"9","author":"Su","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"R93","DOI":"10.1530\/JME-19-0153","article-title":"Circadian clock genes and the transcriptional architecture of the clock mechanism","volume":"63","author":"Cox","year":"2019","journal-title":"J. Mol. Endocrinol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2689600","DOI":"10.1155\/2021\/2689600","article-title":"The link between circadian clock genes and autophagy in chronic obstructive pulmonary disease","volume":"2021","author":"Hu","year":"2021","journal-title":"Mediat. Inflamm."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1161\/CIRCRESAHA.108.191270","article-title":"MicroRNAs as novel regulators of angiogenesis","volume":"104","author":"Sessa","year":"2009","journal-title":"Circ. Res."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1016\/j.neuron.2007.05.017","article-title":"microRNA modulation of circadian-clock period and entrainment","volume":"54","author":"Cheng","year":"2007","journal-title":"Neuron"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Shende, V.R., Neuendorff, N., and Earnest, D.J. (2013). Role of miR-142-3p in the post-transcriptional regulation of the clock gene Bmal1 in the mouse SCN. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0065300"},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Shende, V.R., Goldrick, M.M., Ramani, S., and Earnest, D.J. (2011). Expression and rhythmic modulation of circulating microRNAs targeting the clock gene Bmal1 in mice. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0022586"},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Tan, X., Zhang, P., Zhou, L., Yin, B., Pan, H., and Peng, X. (2012). Clock-controlled mir-142-3p can target its activator, Bmal1. BMC Mol. Biol., 13.","DOI":"10.1186\/1471-2199-13-27"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"3720","DOI":"10.1096\/fj.13-232678","article-title":"Up-regulation of microRNA-142 in simian immunodeficiency virus encephalitis leads to repression of sirtuin1","volume":"27","author":"Chaudhuri","year":"2013","journal-title":"FASEB J."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"4203","DOI":"10.1016\/j.febslet.2012.10.023","article-title":"MiR-34a is involved in Tat-induced HIV-1 long terminal repeat (LTR) transactivation through the SIRT1\/NF\u03baB pathway","volume":"586","author":"Zhang","year":"2012","journal-title":"FEBS Lett."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1957","DOI":"10.1261\/rna.7135204","article-title":"Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs","volume":"10","author":"Cai","year":"2004","journal-title":"Rna"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"45444","DOI":"10.18632\/oncotarget.9989","article-title":"Analysis of clock gene-miRNA correlation networks reveals candidate drivers in colorectal cancer","volume":"7","author":"Mazzoccoli","year":"2016","journal-title":"Oncotarget"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Hasakova, K., Reis, R., Vician, M., Zeman, M., and Herichova, I. (2019). Expression of miR-34a-5p is up-regulated in human colorectal cancer and correlates with survival and clock gene PER2 expression. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0224396"},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Hicks, S.D., Khurana, N., Williams, J., Dowd Greene, C., Uhlig, R., and Middleton, F.A. (2018). Diurnal oscillations in human salivary microRNA and microbial transcription: Implications for human health and disease. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0198288"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1093\/abbs\/gmu007","article-title":"MiR-29a\/b\/c regulate human circadian gene hPER1 expression by targeting its 3\u2032UTR","volume":"46","author":"Zhao","year":"2014","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"12812","DOI":"10.1073\/pnas.1507094112","article-title":"Endothelial miR-17\u223c92 cluster negatively regulates arteriogenesis via miRNA-19 repression of WNT signaling","volume":"112","author":"Qiu","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"D149","DOI":"10.1093\/nar\/gkm995","article-title":"The microRNA. org resource: Targets and expression","volume":"36","author":"Betel","year":"2008","journal-title":"Nucleic Acids Res."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"30070","DOI":"10.1038\/srep30070","article-title":"A novel role of microRNA 17-5p in the modulation of circadian rhythm","volume":"6","author":"Gao","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1126\/science.1136319","article-title":"Suppression of microRNA-silencing pathway by HIV-1 during virus replication","volume":"315","author":"Triboulet","year":"2007","journal-title":"Science"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"5447","DOI":"10.1111\/j.1742-4658.2009.07229.x","article-title":"The miRNA-192\/194 cluster regulates the Period gene family and the circadian clock","volume":"276","author":"Nagel","year":"2009","journal-title":"FEBS J."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"638","DOI":"10.3858\/emm.2009.41.9.070","article-title":"Comprehensive analysis of microRNA-mRNA co-expression in circadian rhythm","volume":"41","author":"Na","year":"2009","journal-title":"Exp. Mol. Med."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/1742-4690-9-5","article-title":"Relationships of PBMC microRNA expression, plasma viral load, and CD4+ T-cell count in HIV-1-infected elite suppressors and viremic patients","volume":"9","author":"Witwer","year":"2012","journal-title":"Retrovirology"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"e2020454118","DOI":"10.1073\/pnas.2020454118","article-title":"A genome-wide microRNA screen identifies the microRNA-183\/96\/182 cluster as a modulator of circadian rhythms","volume":"118","author":"Zhou","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1104\/pp.19.00710","article-title":"A natural variant of miR397 mediates a feedback loop in circadian rhythm","volume":"182","author":"Feng","year":"2020","journal-title":"Plant Physiol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1959","DOI":"10.1016\/j.cub.2013.08.005","article-title":"miRNAs are required for generating a time delay critical for the circadian oscillator","volume":"23","author":"Chen","year":"2013","journal-title":"Curr. Biol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"E8855","DOI":"10.1073\/pnas.1706611114","article-title":"Period2 3\u2032-UTR and microRNA-24 regulate circadian rhythms by repressing PERIOD2 protein accumulation","volume":"114","author":"Yoo","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Chinnapaiyan, S., Dutta, R.K., Devadoss, D., Chand, H.S., Rahman, I., and Unwalla, H.J. (2020). Role of non-coding RNAs in lung circadian clock related diseases. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21083013"},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Datta Chaudhuri, A., Yelamanchili, S.V., and Fox, H.S. (2013). MicroRNA-142 reduces monoamine oxidase A expression and activity in neuronal cells by downregulating SIRT1. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0079579"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"112090","DOI":"10.1016\/j.biopha.2021.112090","article-title":"Gene-specific MicroRNA antagonism protects against HIV Tat and TGF-beta-mediated suppression of CFTR mRNA and function","volume":"142","author":"Dutta","year":"2021","journal-title":"Biomed Pharm."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/11\/9140\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:40:15Z","timestamp":1760125215000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/11\/9140"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,23]]},"references-count":123,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2023,6]]}},"alternative-id":["ijms24119140"],"URL":"https:\/\/doi.org\/10.3390\/ijms24119140","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,23]]}}}