Bioinformatically analyzed relationships between specific human genes associated with HIV attachment

封面

如何引用文章

全文:

详细

Introduction. Assessing interaction between the human immunodeficiency virus (HIV) and human factors is crucial for understanding the disease pathogenesis. HIV triggers an immune response that involves numerous cellular and molecular processes related to inflammation, cell migration, and disrupted tissue barrier functions. Such reactions build up a cascade in which chemokines and cognate co-receptors, as well as other molecules regulating the immune response, play a key role. However, the interaction between HIV and the human organism cannot be reduced to a simple mechanism because it represents a multilayered system where crucial molecules and events may be unknown or require further study. Objective: to assess a significance of candidate genes potentially involved in the pathogenesis of HIV infection during the phase of viral attachment to cell, based on assessing gene expression, localization, and involvement in biological pathways and processes. Materials and methods. The study compared the characteristics of the 100 most promising candidate genes (CG) according to the HumanNet web resource with background genes (CCR5, CXCR4, CCR2, CD4), known to be reliably linked to HIV attachment. Expression data, localization, and involvement in various cellular pathways and processes for the candidate and background genes were analyzed. A scoring system was developed to assess the significance of each gene in the context of its role in immune and inflammatory responses. Results. A total of 100 candidate genes were analyzed. Using the developed scoring system, a number of genes were identified as significant based on the analyzed parameter: 17 candidates — significant by expression profile; 7 — by localization; 17 — by involvement in biological pathways; and 25 — by involvement in biological processes. The final ranking revealed 55 candidate genes. The identified candidate genes were classified into the following functional groups: chemokine co-receptors and their ligands; genes and proteins associated with G-proteins; and a group for which a common functional role or family could not be established. Conclusions. The identified correlations between the candidate genes and background genes highlight the need to further investigate CG interactions in HIV pathogenesis allowing for a more detailed assessment of the contribution of both individual genes and entire systems, which, in the future, will expand our understanding of the molecular mechanisms behind HIV infection and, hypothetically, accelerate the discovery of new (or the expansion of existing) therapeutic models.

作者简介

Vladimir Davydenko

St. Petersburg Pasteur Institute

编辑信件的主要联系方式.
Email: vladimir_david@mail.ru

Junior Researcher, Laboratory of Immunology and Virology of HIV Infection, PhD Student

俄罗斯联邦, St. Petersburg

Yu. Ostankova

St. Petersburg Pasteur Institute

Email: vladimir_david@mail.ru

PhD (Biology), Head of the Laboratory of Immunology and Virology HIV-Infection; Senior Researcher, Laboratory of Molecular Immunology

俄罗斯联邦, St. Petersburg

A. Schemelev

St. Petersburg Pasteur Institute

Email: vladimir_david@mail.ru

Junior Researcher, Laboratory of Immunology and Virology of HIV Infection

俄罗斯联邦, St. Petersburg

E. Anufrieva

St. Petersburg Pasteur Institute

Email: vladimir_david@mail.ru

Junior Researcher, Laboratory of Immunology and Virology of HIV Infection

俄罗斯联邦, St. Petersburg

V. Kushnareva

St. Petersburg Pasteur Institute

Email: vladimir_david@mail.ru

Research Laboratory Assistant, Laboratory of Immunology and Virology of HIV Infection

俄罗斯联邦, St. Petersburg

A. Totolian

St. Petersburg Pasteur Institute; I. Pavlov First St. Petersburg State Medical University

Email: vladimir_david@mail.ru

RAS Full Member, DSc (Medicine), Professor, Head of the Laboratory of Molecular Immunology, Director; Head of the Department of Immunology

俄罗斯联邦, St. Petersburg; St. Petersburg

参考

  1. Aantaa R., Marjamäki A., Scheinin M. Molecular pharmacology of alpha 2-adrenoceptor subtypes. Ann. Med., 1995, vol. 27, no. 4, pp. 439–449. doi: 10.3109/07853899709002452
  2. Al-Ali H.N., Crichton S.J., Fabian C., Pepper C., Butcher D.R., Dempsey F.C., Parris C.N. A therapeutic antibody targeting annexin-A1 inhibits cancer cell growth in vitro and in vivo. Oncogene, 2024, vol. 43, no. 8, pp. 608–614. doi: 10.1038/s41388-023-02919-9
  3. Alkhatib G., Berger E.A. HIV coreceptors: from discovery and designation to new paradigms and promise. Eur. J. Med. Res., 2007, vol. 12, no. 9, pp. 375–384.
  4. Alrumaihi F. The multi-functional roles of CCR7 in human immunology and as a promising therapeutic target for cancer therapeutics. Front. Mol. Biosci., 2022, vol. 9: 834149. doi: 10.3389/fmolb.2022.834149
  5. Apryatin S.A., Rakhmanaliev E.R., Nikolaeva I.A., Ruban S.V., Vazykhova F.G., Klimov E.A., Sulimova G.E., Sidorovich I.G. Comparison of CCR5del32 mutation in the CCR5 gene frequencies in russians, tuvinians, and in groups of HIV-infected individuals. Russian Journal of Genetics, 2005, vol. 41, pp. 1287–1290. doi: 10.1007/s11177-005-0230-6
  6. Aseev M.V., Shawi A., Baranov V.S., Dean M. Population frequencies of the CKR5 mutant allele of the chemokine receptor gene responsible for HIV infection. Russian Journal of Genetics, 1997, vol. 33, no. 12, pp. 1475–1477.
  7. Brandum E.P., Jørgensen A.S., Rosenkilde M.M., Hjortø G.M. Dendritic cells and CCR7 expression: an important factor for autoimmune diseases, chronic inflammation, and cancer. Int. J. Mol. Sci., 2021, vol. 22, no. 8340. doi: 10.3390/ijms22158340
  8. Cannavo A., Liccardo D., Komici K., Corbi G., de Lucia C., Femminella G.D., Elia A., Bencivenga L., Ferrara N., Koch W.J., Paolocci N., Rengo G. Sphingosine kinases and sphingosine 1-phosphate receptors: signaling and actions in the cardiovascular system. Front. Pharmacol., 2017, vol. 8: 556. doi: 10.3389/fphar.2017.00556
  9. Clark-Lewis I., Kim K.S., Rajarathnam K., Gong J.H., Dewald B., Moser B., Baggiolini M., Sykes B.D. Structure-activity relationships of chemokines. J. Leukoc. Biol., 1995, vol. 57, no. 5, pp. 703–711. doi: 10.1002/jlb.57.5.703
  10. Collins P.J., McCully M.L., Martínez-Muñoz L., Santiago C., Wheeldon J., Caucheteux S., Thelen S., Cecchinato V., Laufer J.M., Purvanov V., Monneau Y.R., Lortat-Jacob H., Legler D.F., Uguccioni M., Thelen M., Piguet V., Mellado M., Moser B. Epithelial chemokine CXCL14 synergizes with CXCL12 via allosteric modulation of CXCR4. FASEB J., 2017, vol. 31, no. 7, pp. 3084–3097. doi: 10.1096/fj.201700013R
  11. Console-Bram L., Brailoiu E., Brailoiu G.C., Sharir H., Abood M.E. GPR18 and intracellular calcium, MAPK, β-arrestin. Br. J. Pharmacol., 2014, vol. 171, pp. 3908–3917. doi: 10.1111/bph.12746
  12. Dattilo M., Neuman I., Muñoz M., Maloberti P., Cornejo Maciel F. OxeR1 regulates angiotensin II and cAMP-stimulated steroid production in human H295R adrenocortical cells. Mol. Cell. Endocrinol., 2015, vol. 408, pp. 38–44. doi: 10.1016/j.mce.2015.01.040
  13. Feniger-Barish R., Belkin D., Zaslaver A., Gal S., Dori M., Ran M., Ben-Baruch A. GCP-2-induced internalization of IL-8 receptors: hierarchical relationships between GCP-2 and other ELR(+)-CXC chemokines and mechanisms regulating CXCR2 internalization and recycling. Blood, 2000, vol. 95, no. 5, pp. 1551–1559. doi: 10.1182/blood.V95.5.1551.005a36_1551_1559
  14. Frade J.M., Llorente M., Mellado M., Alcamí J., Gutiérrez-Ramos J.C., Zaballos A., Real G., Martínez-A C. The amino-terminal domain of the CCR2 chemokine receptor acts as coreceptor for HIV-1 infection. J. Clin. Invest., 1997, vol. 100, no. 3, pp. 497–502. doi: 10.1172/JCI119558
  15. Gordon S.B., Read R.C. Macrophage defences against respiratory tract infections. Br. Med. Bull., 2002, vol. 61, pp. 45–61. doi: 10.1093/bmb/61.1.45
  16. Global HIV & AIDS statistics — Fact sheet / UNAIDS 2023 epidemiological estimates. URL: https://www.unaids.org/en/resources/fact-sheet (08.05.2024)
  17. Hernandez P.A., Gorlin R.J., Lukens J.N., Taniuchi S., Bohinjec J., Francois F., Klotman M.E., Diaz G.A. Mutations in the chemokine receptor gene CXCR4 are associated with WHIM syndrome, a combined immunodeficiency disease. Nature Genetics, 2003, vol. 34, no. 1, pp. 70–74. doi: 10.1038/ng1149
  18. Ito Y., Grivel J.C., Chen S., Kiselyeva Y., Reichelderfer P., Margolis L. CXCR4-tropic HIV-1 suppresses replication of CCR5-tropic HIV-1 in human lymphoid tissue by selective induction of CC-chemokines. J. Infect. Dis., 2004, vol. 189, no. 3, pp. 506–514. doi: 10.1086/381153
  19. Ivanov S., Lagunin A., Filimonov D., Tarasova O. Network-based analysis of OMICs data to understand the HIV-host interaction. Front. Microbiol., 2020, vol. 11: 1314. doi: 10.3389/fmicb.2020.01314
  20. Juno J.A., Fowke K.R. Clarifying the role of G protein signaling in HIV infection: new approaches to an old question. AIDS Rev., 2010, vol. 12, no. 3, pp. 164–176.
  21. Keiran N., Ceperuelo-Mallafré V., Calvo E., Hernández-Alvarez M.I., Ejarque M., Núñez-Roa C., Horrillo D., Maymó-Masip E., Rodríguez M.M., Fradera R., de la Rosa J.V., Jorba R., Megia A., Zorzano A., Medina-Gómez G., Serena C., Castrillo A., Vendrell J., Fernández-Veledo S. SUCNR1 controls an anti-inflammatory program in macrophages to regulate the metabolic response to obesity. Nat. Immunol., 2019, vol. 20, no. 5, pp. 581–592. doi: 10.1038/s41590-019-0372-7
  22. Kiertiburanakul S., Sungkanuparph S. Emerging of HIV drug resistance: epidemiology, diagnosis, treatment and prevention. Curr. HIV Res., 2009, vol. 7, no. 3, pp. 273–278. doi: 10.2174/157016209788347976
  23. Kim C.Y., Baek S., Cha J., Yang S., Kim E., Marcotte E.M., Hart T., Lee I. HumanNet v3: an improved database of human gene networks for disease research. Nucleic Acids Res., 2022, vol. 50, no. D1, pp. D632–D639. doi: 10.1093/nar/gkab1048
  24. Kim S.D., Kim J.M., Jo S.H., Lee H.Y., Lee S.Y., Shim J.W., Seo S.K., Yun J., Bae Y.S. Functional expression of formyl peptide receptor family in human NK cells. J. Immunol., 2009, vol. 183, no. 9, pp. 5511–5517. doi: 10.4049/jimmunol.0802986
  25. Koenen J., Bachelerie F., Balabanian K., Schlecht-Louf G., Gallego C. Atypical chemokine receptor 3 (ACKR3): a comprehensive overview of its expression and potential roles in the immune system. Mol. Pharmacol., 2019, vol. 96, no. 6, pp. 809–818. doi: 10.1124/mol.118.115329
  26. Kohlmeier J.E., Cookenham T., Miller S.C., Roberts A.D., Christensen J.P., Thomsen A.R., Woodland D.L. CXCR3 directs antigen-specific effector CD4+ T cell migration to the lung during parainfluenza virus infection. J. Immunol., 2009, vol. 183, no. 7, pp. 4378–4384. doi: 10.4049/jimmunol.0902022
  27. Kurnik D., Muszkat M., Friedman E.A., Sofowora G.G., Diedrich A., Xie H.G., Harris P.A., Choi L., Wood A.J., Stein C.M. Effect of the alpha2C-adrenoreceptor deletion322-325 variant on sympathetic activity and cardiovascular measures in healthy subjects. J. Hypertens., 2007, vol. 25, no. 4, pp. 763–771. doi: 10.1097/HJH.0b013e328017f6e9
  28. Mabrouk N., Tran T., Sam I., Pourmir I., Gruel N., Granier C., Pineau J., Gey A., Kobold S., Fabre E., Tartour E. CXCR6 expressing T cells: functions and role in the control of tumors. Front. Immunol., 2022, vol. 13: 1022136. doi: 10.3389/fimmu.2022.1022136
  29. Mabuka J.M., Mackelprang R.D., Lohman-Payne B., Majiwa M., Bosire R., John-Stewart G., Rowland-Jones S., Overbaugh J., Farquhar C. CCR2-64I polymorphism is associated with lower maternal HIV-1 viral load and reduced vertical HIV-1 transmission. J. Acquir. Immune Defic. Syndr., 2009, vol. 51, no. 2, pp. 235–237. doi: 10.1097/QAI.0b013e31819c155b
  30. Martens K., Steelant B., Bullens D.M.A. Taste receptors: the gatekeepers of the airway epithelium. Cells, 2021, vol. 10, no. 11: 2889. doi: 10.3390/cells10112889
  31. McMyn N.F., Varriale J., Fray E.J., Zitzmann C., MacLeod H., Lai J., Singhal A., Moskovljevic M., Garcia M.A., Lopez B.M., Hariharan V., Rhodehouse K., Lynn K., Tebas P., Mounzer K., Montaner L.J., Benko E., Kovacs C., Hoh R., Simonetti F.R., Laird G.M., Deeks S.G., Ribeiro R.M., Perelson A.S., Siliciano R.F., Siliciano J.M. The latent reservoir of inducible, infectious HIV-1 does not decrease despite decades of antiretroviral therapy. J. Clin. Invest., 2023, vol. 133, no. 17: e171554. doi: 10.1172/JCI171554
  32. Na J., Zhou W., Yin M., Hu Y., Ma X. GNA13 promotes the proliferation and migration of lung squamous cell carcinoma cells through regulating the PI3K/AKT signaling pathway. Tissue Cell, 2022, vol. 76: 101795. doi: 10.1016/j.tice.2022.101795
  33. Nemes B., Bölcskei K., Kecskés A., Kormos V., Gaszner B., Aczél T., Hegedüs D., Pintér E., Helyes Z., Sándor Z. Human somatostatin SST4 receptor transgenic mice: construction and brain expression pattern characterization. Int. J. Mol. Sci., 2021, vol. 22, no. 7: 3758. doi: 10.3390/ijms22073758
  34. Ruckriegl S., Loris J., Wert K., Bauerschmitz G., Gallwas J., Gründker C. Knockdown of G protein-coupled estrogen receptor 1 (GPER1) enhances tumor-supportive properties in cervical carcinoma cells. Cancer Genomics Proteomics, 2023, vol. 20, no. 3, pp. 281–297. doi: 10.21873/cgp.20381
  35. Schafer C.T., Chen Q., Tesmer J.J.G., Handel T.M. Atypical chemokine receptor 3 “senses” CXC chemokine receptor 4 activation through GPCR kinase phosphorylation. Mol. Pharmacol., 2023, vol. 104, no. 4, pp. 174–186. doi: 10.1124/molpharm.123.000710
  36. Schemelev A.N., Davydenko V.S., Ostankova Y.V., Reingardt D.E., Serikova E.N., Zueva E.B., Totolian A.A. Involvement of human cellular proteins and structures in realization of the HIV life cycle: a comprehensive review. Viruses, 2024, vol. 16, no. 11: 1682. doi: 10.3390/v16111682
  37. Shchemelev A.N., Ostankova Y.V., Zueva E.B., Semenov A.V., Totolian A.A. Detection of patient HIV-1 drug resistance mutations in Russia’s Northwestern Federal District in patients with treatment failure. Diagnostics (Basel), 2022, vol. 12, no. 8: 1821. doi: 10.3390/diagnostics12081821
  38. Shimizu T., De Wispelaere A., Winkler M., D’Souza T., Caylor J., Chen L., Dastvan F., Deou J., Cho A., Larena-Avellaneda A., Reidy M., Daum G. Sphingosine-1-phosphate receptor 3 promotes neointimal hyperplasia in mouse iliac-femoral arteries. Arterioscler. Thromb. Vasc. Biol., 2012, vol. 32, no. 4, pp. 955–961. doi: 10.1161/ATVBAHA.111.241034
  39. Spathakis M., Dovrolis N., Filidou E., Kandilogiannakis L., Tarapatzi G., Valatas V., Drygiannakis I., Paspaliaris V., Arvanitidis K., Manolopoulos V.G., Kolios G., Vradelis S. Exploring microbial metabolite receptors in inflammatory bowel disease: an in silico analysis of their potential role in inflammation and fibrosis. Pharmaceuticals (Basel), 2024, vol. 17, no. 492. doi: 10.3390/ph17040492
  40. Steiniger B., Barth P., Hellinger A. The perifollicular and marginal zones of the human splenic white pulp: do fibroblasts guide lymphocyte immigration? Am. J. Pathol., 2001, vol. 159, no. 2, pp. 501–512. doi: 10.1016/S0002-9440(10)61722-1
  41. Tsou C.L., Peters W., Si Y., Slaymaker S., Aslanian A.M., Weisberg S.P., Mack M., Charo I.F. Critical roles for CCR2 and MCP-3 in monocyte mobilization from bone marrow and recruitment to inflammatory sites. J. Clin. Invest., 2007, vol. 117, no. 4, pp. 902–909. doi: 10.1172/JCI29919
  42. Van Op den Bosch J., Torfs P., De Winter B.Y., De Man J.G., Pelckmans P.A., Van Marck E., Grundy D., Van Nassauw L., Timmermans J.P. Effect of genetic SSTR4 ablation on inflammatory peptide and receptor expression in the non-inflamed and inflamed murine intestine. J. Cell. Mol. Med., 2009, vol. 13, no. 9B, pp. 3283–3295. doi: 10.1111/j.1582-4934.2009.00760.x
  43. Wareing M.D., Lyon A.B., Lu B., Gerard C., Sarawar S.R. Chemokine expression during the development and resolution of a pulmonary leukocyte response to influenza A virus infection in mice. J. Leukoc. Biol., 2004, vol. 76, no. 4, pp. 886–895. doi: 10.1189/jlb.1203644
  44. Xu Z., Gong L., Peng P., Liu Y., Xue C., Cao Y. Porcine enteric alphacoronavirus inhibits IFN-α, IFN-β, OAS, Mx1, and PKR mRNA expression in infected Peyer’s patches in vivo. Front. Vet. Sci., 2020, vol. 7: 449. doi: 10.3389/fvets.2020.00449
  45. Yagensky O., Kohansal-Nodehi M., Gunaseelan S., Rabe T., Zafar S., Zerr I., Härtig W., Urlaub H., Chua J.J. Increased expression of heme-binding protein 1 early in Alzheimer’s disease is linked to neurotoxicity. Elife, 2019, vol. 8: e47498. doi: 10.7554/eLife.47498
  46. Yan Y., Chen R., Wang X., Hu K., Huang L., Lu M., Hu Q. CCL19 and CCR7 expression, signaling pathways, and adjuvant functions in viral infection and prevention. Front. Cell Dev. Biol., 2019, vol. 7: 212. doi: 10.3389/fcell.2019.00212

补充文件

附件文件
动作
1. JATS XML
下载
2. Figure 1. Study design

下载 (279KB)
索引源数据
3. Figure 2. AUROC prediction of identified HumanNet candidate genes, calculated relative to background genes (CCR5, CXCR4, CD4, CCR2) with a false-positive rate cutoff of 1%

下载 (91KB)
索引源数据
4. Figure 3. Tissue-specific expression map for background genes (CCR5, CXCR4, CD4, CCR2) and candidate genes (CGs). CCR5, CXCR4, CD4, and CCR2 are highlighted with a red border

下载 (1008KB)
索引源数据
5. Figure 4. Localization of gene products. Candidate genes (CGs) are presented along the horizontal axis, while cell types and/or their structures are on the vertical axis. Background genes (CCR5, CXCR4, CD4, CCR2) are marked with a red border

下载 (196KB)
索引源数据
6. Figure 5. Biological pathway annotation for BG, CG, their proteins, and metabolites (p < 0.05). CG are represented on the horizontal axis; biological pathways are on the vertical axis. BG (CCR5, CXCR4, CD4, CCR) are marked. Analysis obtained in GENE2FUNC mode using WikiPathways data

下载 (178KB)
索引源数据

版权所有 © Davydenko V.S., Ostankova Y.V., Schemelev A.N., Anufrieva E.V., Kushnareva V.V., Totolian A.A., 2024

Creative Commons License
此作品已接受知识共享署名 4.0国际许可协议的许可

Согласие на обработку персональных данных с помощью сервиса «Яндекс.Метрика»

1. Я (далее – «Пользователь» или «Субъект персональных данных»), осуществляя использование сайта https://journals.rcsi.science/ (далее – «Сайт»), подтверждая свою полную дееспособность даю согласие на обработку персональных данных с использованием средств автоматизации Оператору - федеральному государственному бюджетному учреждению «Российский центр научной информации» (РЦНИ), далее – «Оператор», расположенному по адресу: 119991, г. Москва, Ленинский просп., д.32А, со следующими условиями.

2. Категории обрабатываемых данных: файлы «cookies» (куки-файлы). Файлы «cookie» – это небольшой текстовый файл, который веб-сервер может хранить в браузере Пользователя. Данные файлы веб-сервер загружает на устройство Пользователя при посещении им Сайта. При каждом следующем посещении Пользователем Сайта «cookie» файлы отправляются на Сайт Оператора. Данные файлы позволяют Сайту распознавать устройство Пользователя. Содержимое такого файла может как относиться, так и не относиться к персональным данным, в зависимости от того, содержит ли такой файл персональные данные или содержит обезличенные технические данные.

3. Цель обработки персональных данных: анализ пользовательской активности с помощью сервиса «Яндекс.Метрика».

4. Категории субъектов персональных данных: все Пользователи Сайта, которые дали согласие на обработку файлов «cookie».

5. Способы обработки: сбор, запись, систематизация, накопление, хранение, уточнение (обновление, изменение), извлечение, использование, передача (доступ, предоставление), блокирование, удаление, уничтожение персональных данных.

6. Срок обработки и хранения: до получения от Субъекта персональных данных требования о прекращении обработки/отзыва согласия.

7. Способ отзыва: заявление об отзыве в письменном виде путём его направления на адрес электронной почты Оператора: info@rcsi.science или путем письменного обращения по юридическому адресу: 119991, г. Москва, Ленинский просп., д.32А

8. Субъект персональных данных вправе запретить своему оборудованию прием этих данных или ограничить прием этих данных. При отказе от получения таких данных или при ограничении приема данных некоторые функции Сайта могут работать некорректно. Субъект персональных данных обязуется сам настроить свое оборудование таким способом, чтобы оно обеспечивало адекватный его желаниям режим работы и уровень защиты данных файлов «cookie», Оператор не предоставляет технологических и правовых консультаций на темы подобного характера.

9. Порядок уничтожения персональных данных при достижении цели их обработки или при наступлении иных законных оснований определяется Оператором в соответствии с законодательством Российской Федерации.

10. Я согласен/согласна квалифицировать в качестве своей простой электронной подписи под настоящим Согласием и под Политикой обработки персональных данных выполнение мною следующего действия на сайте: https://journals.rcsi.science/ нажатие мною на интерфейсе с текстом: «Сайт использует сервис «Яндекс.Метрика» (который использует файлы «cookie») на элемент с текстом «Принять и продолжить».