Russian Journal of Infection and ImmunityRussian Journal of Infection and ImmunityИнфекция и иммунитет2220-76192313-7398SPb RAACI1783010.15789/2220-7619-BAR-17830ORIGINAL ARTICLESОРИГИНАЛЬНЫЕ СТАТЬИResearch ArticleBioinformatically analyzed relationships between specific human genes associated with HIV attachmentБиоинформатический анализ взаимосвязей между специфическими генами человека, ассоциированными с прикреплением ВИЧDavydenkoVladimir S.ДавыденкоВладимир Сергеевич
Russian Federation

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

младший научный сотрудник лаборатории иммунологии и вирусологии ВИЧ-инфекции, аспирант

vladimir_david@mail.ruOstankovaYu. V.ОстанковаЮ. В.
Russian Federation

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

к.б.н., зав. лабораторией иммунологии и вирусологии ВИЧ-инфекции; старший научный сотрудник лаборатории молекулярной иммунологии

vladimir_david@mail.ruSchemelevA. N.ЩемелевА. Н.
Russian Federation

Junior Researcher, Laboratory of Immunology and Virology of HIV Infection

младший научный сотрудник лаборатории иммунологии и вирусологии ВИЧ-инфекции

vladimir_david@mail.ruAnufrievaE. V.АнуфриеваЕ. В.
Russian Federation

Junior Researcher, Laboratory of Immunology and Virology of HIV Infection

младший научный сотрудник лаборатории иммунологии и вирусологии ВИЧ-инфекции

vladimir_david@mail.ruKushnarevaV. V.КушнареваВ. В.
Russian Federation

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

лаборант-исследователь лаборатории иммунологии и вирусологии ВИЧ-инфекции

vladimir_david@mail.ruTotolianA. A.ТотолянА. А.
Russian Federation

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

академик РАН, д.м.н., профессор, зав. лабораторией молекулярной иммунологии, директор; зав. кафедрой иммунологии

vladimir_david@mail.ruSt. Petersburg Pasteur InstituteФБУН НИИ эпидемиологии и микробиологии имени ПастераI. Pavlov First St. Petersburg State Medical UniversityФГБОУ ВО Первый Санкт-Петербургский государственный медицинский университет имени академика И.П. Павлова МЗ РФ1812202425122024146115311680412202411122024Copyright ©; 2024, Davydenko V.S., Ostankova Y.V., Schemelev A.N., Anufrieva E.V., Kushnareva V.V., Totolian A.A.Copyright ©; 2024, Давыденко В.С., Останкова Ю.В., Щемелев А.Н., Ануфриева Е.В., Кушнарева В.В., Тотолян А.А.2024Davydenko V.S., Ostankova Y.V., Schemelev A.N., Anufrieva E.V., Kushnareva V.V., Totolian A.A.Давыденко В.С., Останкова Ю.В., Щемелев А.Н., Ануфриева Е.В., Кушнарева В.В., Тотолян А.А.https://creativecommons.org/licenses/by/4.0https://iimmun.ru/iimm/article/view/17830

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.

Введение. Изучение взаимодействия вируса иммунодефицита человека (ВИЧ) с факторами человеческого организма имеет ключевое значение для понимания патогенеза заболевания. ВИЧ вызывает иммунную реакцию, которая включает в себя множество клеточных и молекулярных процессов, связанных с воспалением, миграцией клеток и нарушением барьерных функций тканей. Эти реакции образуют каскад, в котором важную роль играют как хемокины и их корецепторы, так и другие молекулы, регулирующие иммунный ответ. Проблема состоит в том, что взаимодействие ВИЧ с человеческим организмом невозможно свести к простому механизму — это сложная система, в которой ключевые молекулы и механизмы могут быть неизвестны и требуют дальнейшего изучения. Целью исследования была оценка значимости генов-кандидатов, потенциально участвующих в патогенезе ВИЧ-инфекции на стадии прикрепления вируса к клетке, на основании оценки экспрессии, локализации и участии в биологических путях и процессах. Материалы и методы. В работе было проведено сравнение характеристик 100 наиболее перспективных генов-кандидатов (ГК) согласно веб-ресурсу HumanNet с фоновыми генами (CCR5, CXCR4, CCR2, CD4), для которых достоверно показана связь с прикреплением ВИЧ к клетке. Были проанализированы данные экспрессии, локализации, а также вовлеченности в различные клеточные пути и процессы генов-кандидатов и фоновых генов. В ходе работы была разработана система баллового ранжирования, которая позволила оценить значимость каждого гена в контексте его участия в иммунных и воспалительных реакциях. Результаты. Проанализировано 100 генов-кандидатов. С использованием разработанного метода баллового ранжирования ряд генов был определен, как значимый в зависимости от анализируемой характеристики: значимые по профилю экспрессии — 17 кандидатов, локализации — 7, участие в биологических путях — 17, в биологических процессах — 25. По результатам итогового ранжирования выявлено 55 ГК. Выявленные ГК были отнесены к следующим функциональным группам: хемокиновые корецепторы и их лиганды, гены и белки, связанные с G-белками, а также группа, для членов которой не удалось установить общую функциональную роль или семейство. Выводы. Выявленные корреляции между ГК и фоновыми генами акцентируют внимание на необходимости дальнейшего изучения взаимодействий ГК в патогенезе ВИЧ. Это позволит более детально оценить вклад как отдельных генов, так и целых систем, что, в дальнейшем, расширит наше понимание молекулярных механизмов ВИЧ-инфекции, а также, гипотетически, ускорит обнаружение новых или расширение существующих терапевтических моделей.

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