Background: Two big issues in the study of pathogens are determining how pathogens
infect hosts and how the host defends itself against infection. Therefore, investigating host-pathogen
interactions is important for understanding pathogenicity and host defensive mechanisms and treating
Methods: In this study, we used omics data, including time-course data from high-throughput sequencing,
real-time polymerase chain reaction, and human microRNA (miRNA) and protein-protein
interaction to construct an interspecies protein-protein and miRNA interaction (PPMI) network of
human CD4+ T cells during HIV-1 infection through system modeling and identification.
Results: By applying a functional annotation tool to the identified PPMI network at each stage of
HIV infection, we found that repressions of three miRNAs, miR-140-5p, miR-320a, and miR-941,
are involved in the development of autoimmune disorders, tumor proliferation, and the pathogenesis
of T cells at the reverse transcription stage. Repressions of miR-331-3p and miR-320a are involved
in HIV-1 replication, replicative spread, anti-apoptosis, cell proliferation, and dysregulation of cell
cycle control at the integration/replication stage. Repression of miR-341-5p is involved in carcinogenesis
at the late stage of HIV-1 infection.
Conclusion: By investigating the common core proteins and changes in specific proteins in the
PPMI network between the stages of HIV-1 infection, we obtained pathogenic insights into the functional
core modules and identified potential drug combinations for treating patients with HIV-1 infection,
including thalidomide, oxaprozin, and metformin, at the reverse transcription stage; quercetin,
nifedipine, and fenbendazole, at the integration/replication stage; and staurosporine, quercetin,
prednisolone, and flufenamic acid, at the late stage.