{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T12:58:20Z","timestamp":1763643500776,"version":"3.37.3"},"reference-count":37,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,5,10]],"date-time":"2022-05-10T00:00:00Z","timestamp":1652140800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,5,10]],"date-time":"2022-05-10T00:00:00Z","timestamp":1652140800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>During advanced HIV infection, Human Cytomegalovirus (HCMV) has been proven to produce devitalizing end-organ diseases (EOD). The interactive co-existence of HIV and HCMV has been reported by many researchers and has been suggested to be linked with a more aggressive disease state. This study has been designed to bring forward an assessment of the clinical risk factors capable of defining the conditions of HCMV induced retinitis and gastro-enteric diseases among HIV1 seropositive patients. We also intended to analyse the phylogenetic variation if any, among the infecting virus types inducing the two separate clinical conditions. The patients were arranged in three different groups; (Group 1 with 26 individuals and group 2 and group 3 with 25 individuals each) based on their current status of HIV and HCMV infections. Serum ELISA, qualitative and quantitative detection of HCMV DNA, Real time mRNA expression study, sequencing, and phylogenetic analysis were performed. All statistical analyses and graphs were exercised using relevant software. We found that in HIV patients with HCMV induced end-organ diseases the components of the CXCL9, 10, 11-CXCR3 chemokine pathway is highly expressed with significant differences existing among patients with retinitis and gastrointestinal disease. We found that the gL gene sequences from the retinitis (HR) group clustered almost separately from that of the gastroenteritis (HG) group in the phylogenetic tree. It may be suggested that a form of natural selection pressure is working on the clinical HCMV strains creating a slight divergence in their phylogenetic lineage thereby helping them adapt to the particular tissue microenvironment they are colonizing.<\/jats:p>","DOI":"10.1038\/s41598-022-11727-2","type":"journal-article","created":{"date-parts":[[2022,5,10]],"date-time":"2022-05-10T10:03:22Z","timestamp":1652177002000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A comparative analysis depicting the disease characteristics and phylogenetic signature of human cytomegalovirus infection in Human Immunodeficiency Virus 1 seropositive patients with end-organ retinitis and gastro-enteric diseases"],"prefix":"10.1038","volume":"12","author":[{"given":"Aroni","family":"Chatterjee","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Debsopan","family":"Roy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sumit","family":"Mukherjee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiya","family":"Ghosh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agnibha","family":"Maiti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rivu","family":"Basu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nilanjan","family":"Chakraborty","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,5,10]]},"reference":[{"key":"11727_CR1","doi-asserted-by":"publisher","first-page":"S37","DOI":"10.1097\/00002030-199611000-00009","volume":"10","author":"EF Bowen","year":"1996","unstructured":"Bowen, E. F., Griffiths, P. D., Davey, C. C., Emery, V. C. & Johnson, M. A. Lessons from the natural history of cytomegalovirus. AIDS 10, S37-41 (1996).","journal-title":"AIDS"},{"key":"11727_CR2","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1097\/00042560-199604150-00006","volume":"11","author":"DH Shepp","year":"1996","unstructured":"Shepp, D. H., Moses, J. E. & Kaplan, M. H. Seroepidemiology of cytomegalovirus in patients with advanced HIV disease: Influence on disease expression and survival. J. Acquir. Immune Defic. Syndr. 11, 460\u2013468 (1996).","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"11727_CR3","first-page":"134","volume":"22","author":"NS Lurain","year":"2015","unstructured":"Lurain, N. S. et al. The association of human cytomegalovirus with biomarkers of inflammation and immune activation in HIV-1-infected women. AIDS Res. Hum. Retrovir. 22, 134\u2013143 (2015).","journal-title":"AIDS Res. Hum. Retrovir."},{"issue":"3","key":"11727_CR4","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1007\/s00430-015-0415-0","volume":"204","author":"JG Sissons","year":"2015","unstructured":"Sissons, J. G. & Willis, M. R. How understanding immunology contributes to managing CMV disease in immunosuprpessed patients: Now and in future. Med. Microbiol. Immunol. 204(3), 307\u2013316 (2015).","journal-title":"Med. Microbiol. Immunol."},{"key":"11727_CR5","first-page":"629","volume":"61","author":"RB Podlasin","year":"2007","unstructured":"Podlasin, R. B. CMV infection in HIV-patients. Przegl. Epidemiol. 61, 629\u2013637 (2007).","journal-title":"Przegl. Epidemiol."},{"key":"11727_CR6","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1001\/jama.283.5.653","volume":"283","author":"SM Whitcup","year":"2000","unstructured":"Whitcup, S. M. Cytomegalovirus retinitis in the era of highly antirretroviral therapy. JAMA 283, 653\u2013657 (2000).","journal-title":"JAMA"},{"key":"11727_CR7","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1590\/S1413-86702007000100039","volume":"11","author":"S Majumder","year":"2007","unstructured":"Majumder, S. et al. Multiorgan involvement due to cytomegalovirus infection in AIDS. Braz. J. Infect. Dis. 11, 176\u2013178 (2007).","journal-title":"Braz. J. Infect. Dis."},{"key":"11727_CR8","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1186\/s12955-016-0517-4","volume":"14","author":"S George","year":"2016","unstructured":"George, S., Bergin, C., Clarke, S., Courtney, G. & Codd, M. B. Health-related quality of life and associated factors in people with HIV: An Irish cohort study. Health Qual. Life Outcomes. 14, 115 (2016).","journal-title":"Health Qual. Life Outcomes."},{"key":"11727_CR9","doi-asserted-by":"publisher","first-page":"1497","DOI":"10.1097\/00002030-199908200-00009","volume":"13","author":"JL Casado","year":"1999","unstructured":"Casado, J. L. et al. Incidence and risk factors for developing cytomegalovirus retinitis in HIV-infected patients receiving protease inhibitor theraphy. Spanish CMV-AIDS Study Group. AIDS 13, 1497\u20131502 (1999).","journal-title":"AIDS"},{"key":"11727_CR10","doi-asserted-by":"publisher","first-page":"119","DOI":"10.4103\/2229-516X.157166","volume":"5","author":"K Ramesh","year":"2015","unstructured":"Ramesh, K., Gandhi, S. & Rao, V. Clinical profile of human immunodeficiency virus patients with opportunistic infections: A descriptive case series study. Int. J. Appl. Basic Med. Res. 5, 119\u2013123 (2015).","journal-title":"Int. J. Appl. Basic Med. Res."},{"key":"11727_CR11","first-page":"641","volume":"4","author":"AV Loo","year":"2011","unstructured":"Loo, A. V., Sujaya, S., Peyman, M., Florence, S. & Subrayan, V. Retinal manifestations of patients with immunodeficiency virus, a multiethnics study in Malaysia. Int. J. Ophthalmol. 4, 641\u2013643 (2011).","journal-title":"Int. J. Ophthalmol."},{"key":"11727_CR12","doi-asserted-by":"publisher","first-page":"1452","DOI":"10.1016\/j.ophtha.2015.02.033","volume":"122","author":"DA Jabs","year":"2015","unstructured":"Jabs, D. A. et al. Long-term outcomes of cytomegalovirus retinitis in the era of modern antiretroviral therapy: Results from a United States cohort. Ophthalmology 122, 1452\u20131463 (2015).","journal-title":"Ophthalmology"},{"key":"11727_CR13","doi-asserted-by":"publisher","first-page":"780","DOI":"10.1016\/j.ophtha.2006.11.008","volume":"114","author":"DA Jabs","year":"2007","unstructured":"Jabs, D. A. et al. Longitudinal study of the ocular complications of AIDS: 1. Ocular diagnoses at enrollment. Ophthalmology 114, 780\u2013786 (2007).","journal-title":"Ophthalmology"},{"key":"11727_CR14","doi-asserted-by":"publisher","first-page":"7546","DOI":"10.1167\/iovs.12-10349","volume":"53","author":"SC Teoh","year":"2012","unstructured":"Teoh, S. C., Wang, P. X. & Wong, E. P. The epidemiology and incidence of cytomegalovirus retinitis in the HIV population in Singapore over 6 years. Investig. Ophthalmol. Vis. Sci. 53, 7546\u20137552 (2012).","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"11727_CR15","doi-asserted-by":"publisher","first-page":"1016","DOI":"10.3389\/fmicb.2015.01016","volume":"6","author":"E Adland","year":"2015","unstructured":"Adland, E., Klenerman, P., Goulder, P. & Matthews, P. C. Ongoing burden of disease from HIV\/CMV coinfection in Africa in the antirretroviral theraphy era. Front. Microbiol. 6, 1016 (2015).","journal-title":"Front. Microbiol."},{"key":"11727_CR16","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1097\/COH.0000000000000241","volume":"11","author":"A Boulougoura","year":"2016","unstructured":"Boulougoura, A. & Sereti, I. HIV infection and immune activation: The role of coinfections. Curr. Opin. HIV AIDS. 11, 191\u2013200 (2016).","journal-title":"Curr. Opin. HIV AIDS."},{"key":"11727_CR17","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1186\/s12967-019-02172-3","volume":"17","author":"X Yin","year":"2019","unstructured":"Yin, X. et al. The combination of CXCL9, CXCL10 and CXCL11 levels during primary HIV infection predicts HIV disease progression. J. Transl. Med. 17, 417. https:\/\/doi.org\/10.1186\/s12967-019-02172-3 (2019).","journal-title":"J. Transl. Med."},{"key":"11727_CR18","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.cyto.2018.11.018","volume":"115","author":"J Lei","year":"2019","unstructured":"Lei, J., Yin, X., Shang, H. & Jiang, Y. IP-10 is highly involved in HIV infection. Cytokine 115, 97\u2013103. https:\/\/doi.org\/10.1016\/j.cyto.2018.11.018 (2019) (Epub 2018 Nov 22 PMID: 30472104).","journal-title":"Cytokine"},{"key":"11727_CR19","doi-asserted-by":"publisher","first-page":"004","DOI":"10.4172\/2155-9899.S7-004","volume":"S7","author":"R Mehla","year":"2012","unstructured":"Mehla, R., Guha, D. & Ayyavoo, V. Chemokine deregulation in HIV infection: Role of interferon gamma induced Th1-chemokine signaling. J. Clin. Cell Immunol. S7, 004. https:\/\/doi.org\/10.4172\/2155-9899.S7-004 (2012).","journal-title":"J. Clin. Cell Immunol."},{"key":"11727_CR20","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1016\/j.coviro.2014.08.001","volume":"8","author":"N Renzette","year":"2014","unstructured":"Renzette, N., Gibson, L., Jensen, J. D. & Kowalik, T. F. Human cytomegalovirus intrahost evolution\u2014A new avenue for understanding and controlling herpesvirus infections. Curr. Opin. Virol. 8, 109\u2013115. https:\/\/doi.org\/10.1016\/j.coviro.2014.08.001 (2014) (Epub 2014 Aug 25. PMID: 25154343; PMCID: PMC4195796).","journal-title":"Curr. Opin. Virol."},{"key":"11727_CR21","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1002\/jmv.21459","volume":"81","author":"P Sowmya","year":"2009","unstructured":"Sowmya, P. & Madhavan, H. N. Analysis of mixed infections by multiple genotypes of human cytomegalovirus in immunocompromised patients. J. Med. Virol. 81, 861\u2013869 (2009).","journal-title":"J. Med. Virol."},{"key":"11727_CR22","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1086\/421496","volume":"39","author":"A Coaquette","year":"2004","unstructured":"Coaquette, A. et al. Mixed cytomegalovirus glycoprotein B genotypes in immunocompromised patients. Clin. Infect. Dis. 39, 155\u2013161 (2004).","journal-title":"Clin. Infect. Dis."},{"key":"11727_CR23","doi-asserted-by":"publisher","first-page":"952","DOI":"10.1093\/infdis\/150.6.952","volume":"150","author":"WL Drew","year":"1984","unstructured":"Drew, W. L., Sweet, E. S., Miner, R. C. & Mocarski, E. S. Multiple infections by cytomegalovirus in patients with acquired immunodeficiency syndrome: Documentation by Southern blot hybridization. J. Infect. Dis. 150, 952\u2013953 (1984).","journal-title":"J. Infect. Dis."},{"key":"11727_CR24","doi-asserted-by":"publisher","first-page":"1162","DOI":"10.1086\/515262","volume":"177","author":"U Meyer-K\u00f6nig","year":"1998","unstructured":"Meyer-K\u00f6nig, U., Haberland, M., von Laer, D., Haller, O. & Hufert, F. T. Intragenic variability of human cytomegalovirus glycoprotein B in clinical strains. J. Infect. Dis. 177, 1162\u20131169 (1998).","journal-title":"J. Infect. Dis."},{"issue":"17","key":"11727_CR25","doi-asserted-by":"publisher","first-page":"5201","DOI":"10.1111\/febs.15835","volume":"288","author":"G Carmi","year":"2021","unstructured":"Carmi, G., Gorohovski, A., Mukherjee, S. & Frenkel-Morgenstern, M. Non-optimal codon usage preferences of coronaviruses determine their promiscuity for infecting multiple hosts. FEBS J. 288(17), 5201\u20135223. https:\/\/doi.org\/10.1111\/febs.15835 (2021) (Epub 2021 Apr 7 PMID: 33756061).","journal-title":"FEBS J."},{"issue":"5","key":"11727_CR26","doi-asserted-by":"publisher","first-page":"401","DOI":"10.3390\/v11050401","volume":"11","author":"M Kiening","year":"2019","unstructured":"Kiening, M. et al. Conserved secondary structures in viral mRNAs. Viruses 11(5), 401. https:\/\/doi.org\/10.3390\/v11050401 (2019) (PMID:31035717;PMCID:PMC6563262).","journal-title":"Viruses"},{"issue":"7","key":"11727_CR27","doi-asserted-by":"publisher","first-page":"1257","DOI":"10.1007\/s00467-020-04523-5","volume":"35","author":"A Chatterjee","year":"2020","unstructured":"Chatterjee, A. et al. A cross-sectional study exploring disease characteristics and phylogenetic nature of human cytomegalovirus among infected neonates with congenital nephrotic syndrome. Pediatr. Nephrol. 35(7), 1257\u20131266. https:\/\/doi.org\/10.1007\/s00467-020-04523-5 (2020) (Epub 2020 Mar 13 PMID: 32170428).","journal-title":"Pediatr. Nephrol."},{"issue":"6","key":"11727_CR28","doi-asserted-by":"publisher","first-page":"1767","DOI":"10.1073\/pnas.1424818112","volume":"112","author":"C Ciferri","year":"2015","unstructured":"Ciferri, C. et al. Structural and biochemical studies of HCMV gH\/gL\/gO and Pentamer reveal mutually exclusive cell entry complexes. Proc. Natl. Acad. Sci. U. S. A. 112(6), 1767\u20131772. https:\/\/doi.org\/10.1073\/pnas.1424818112 (2015) (Epub 2015 Jan 26. PMID: 25624487; PMCID: PMC4330774).","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"issue":"37","key":"11727_CR29","doi-asserted-by":"publisher","first-page":"14118","DOI":"10.1073\/pnas.0804365105","volume":"105","author":"BJ Ryckman","year":"2008","unstructured":"Ryckman, B. J., Chase, M. C. & Johnson, D. C. HCMV gH\/gL\/UL128-131 interferes with virus entry into epithelial cells: Evidence for cell type-specific receptors. Proc. Natl. Acad. Sci. USA 105(37), 14118\u201314123 (2008).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"issue":"1","key":"11727_CR30","doi-asserted-by":"publisher","first-page":"15861","DOI":"10.1038\/s41598-020-73009-z.PMID:32985571;PMCID:PMC7522230","volume":"10","author":"A Chatterjee","year":"2020","unstructured":"Chatterjee, A. et al. Insight into the distinctive paradigm of Human Cytomegalovirus associated intrahepatic and extrahepatic cholestasis in neonates. Sci. Rep. 10(1), 15861. https:\/\/doi.org\/10.1038\/s41598-020-73009-z.PMID:32985571;PMCID:PMC7522230 (2020).","journal-title":"Sci. Rep."},{"key":"11727_CR31","doi-asserted-by":"publisher","first-page":"1792","DOI":"10.1093\/nar\/gkh340","volume":"32","author":"RC Edgar","year":"2004","unstructured":"Edgar, R. C. MUSCLE: Multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res. 32, 1792\u20131797. https:\/\/doi.org\/10.1093\/nar\/gkh340 (2004).","journal-title":"Nucleic Acids Res."},{"key":"11727_CR32","doi-asserted-by":"publisher","first-page":"1972","DOI":"10.1093\/bioinformaticsbtp348","volume":"25","author":"S Capella-Guti\u00e9rrez","year":"2009","unstructured":"Capella-Guti\u00e9rrez, S., Silla-Mart\u00ednez, J. M. & Gabald\u00f3n, T. trimAl: A tool for automated alignment trimming in large-scale phylogenetic analyses. Bioinformatics 25, 1972\u20131973. https:\/\/doi.org\/10.1093\/bioinformaticsbtp348 (2009).","journal-title":"Bioinformatics"},{"key":"11727_CR33","doi-asserted-by":"publisher","first-page":"1547","DOI":"10.1093\/molbev\/msy096","volume":"35","author":"S Kumar","year":"2018","unstructured":"Kumar, S., Stecher, G., Li, M., Knyaz, C. & Tamura, K. MEGA X: Molecular evolutionary genetics analysis across computing platforms. Mol. Biol. Evol. 35, 1547\u20131549. https:\/\/doi.org\/10.1093\/molbev\/msy096 (2018).","journal-title":"Mol. Biol. Evol."},{"key":"11727_CR34","doi-asserted-by":"publisher","first-page":"957","DOI":"10.1016\/j.bbrc.2004.03.138","volume":"317","author":"A Fuglsang","year":"2004","unstructured":"Fuglsang, A. The \u2018effective number of codons\u2019 revisited. Biochem. Biophys. Res. Commun. 317, 957\u2013964 (2004).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"11727_CR35","doi-asserted-by":"publisher","first-page":"2098","DOI":"10.1016\/j.meegid.2011.08.025","volume":"11","author":"JS Hu","year":"2011","unstructured":"Hu, J. S. et al. The characteristic of codon usage pattern and its evolution of hepatitis C virus. Infect. Genet. Evol. 11, 2098\u20132102. https:\/\/doi.org\/10.1016\/j.meegid.2011.08.025 (2011).","journal-title":"Infect. Genet. Evol."},{"key":"11727_CR36","doi-asserted-by":"publisher","first-page":"401","DOI":"10.3390\/v11050401","volume":"11","author":"M Kiening","year":"2019","unstructured":"Kiening, M. et al. Conserved secondary structures in viral mRNAs. Viruses 11, 401 (2019).","journal-title":"Viruses"},{"key":"11727_CR37","doi-asserted-by":"publisher","first-page":"900","DOI":"10.1261\/rna.029041.111","volume":"18","author":"S Will","year":"2012","unstructured":"Will, S., Joshi, T., Hofacker, I. L., Stadler, P. F. & Backofen, R. LocARNA-P: Accurate boundary prediction and improved detection of structural RNAs. RNA 18, 900\u2013914. https:\/\/doi.org\/10.1261\/rna.029041.111 (2012).","journal-title":"RNA"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-11727-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-11727-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-11727-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,25]],"date-time":"2022-11-25T02:40:27Z","timestamp":1669344027000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-11727-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,10]]},"references-count":37,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["11727"],"URL":"https:\/\/doi.org\/10.1038\/s41598-022-11727-2","relation":{},"ISSN":["2045-2322"],"issn-type":[{"type":"electronic","value":"2045-2322"}],"subject":[],"published":{"date-parts":[[2022,5,10]]},"assertion":[{"value":"18 November 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 April 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 May 2022","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":"7617"}}