Bioinformatically analyzed relationships between specific human genes associated with HIV attachment

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.