Dataset Information

In silico predictions of protein interactions between Zika virus and human host.

ABSTRACT:

Background

The ZIKA virus (ZIKV) belongs to the Flaviviridae family, was first isolated in the 1940s, and remained underreported until its global threat in 2016, where drastic consequences were reported as Guillan-Barre syndrome and microcephaly in newborns. Understanding molecular interactions of ZIKV proteins during the host infection is important to develop treatments and prophylactic measures; however, large-scale experimental approaches normally used to detect protein-protein interaction (PPI) are onerous and labor-intensive. On the other hand, computational methods may overcome these challenges and guide traditional approaches on one or few protein molecules. The prediction of PPIs can be used to study host-parasite interactions at the protein level and reveal key pathways that allow viral infection.

Results

Applying Random Forest and Support Vector Machine (SVM) algorithms, we performed predictions of PPI between two ZIKV strains and human proteomes. The consensus number of predictions of both algorithms was 17,223 pairs of proteins. Functional enrichment analyses were executed with the predicted networks to access the biological meanings of the protein interactions. Some pathways related to viral infection and neurological development were found for both ZIKV strains in the enrichment analysis, but the JAK-STAT pathway was observed only for strain PE243 when compared with the FSS13025 strain.

Conclusions

The consensus network of PPI predictions made by Random Forest and SVM algorithms allowed an enrichment analysis that corroborates many aspects of ZIKV infection. The enrichment results are mainly related to viral infection, neuronal development, and immune response, and presented differences among the two compared ZIKV strains. Strain PE243 presented more predicted interactions between proteins from the JAK-STAT signaling pathway, which could lead to a more inflammatory immune response when compared with the FSS13025 strain. These results show that the methodology employed in this study can potentially reveal new interactions between the ZIKV and human cells.

SUBMITTER: Pitta JLLP

PROVIDER: S-EPMC8395582 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:To study virus-host protein interactions, knowledge about viral and host protein architectures and repertoires, their particular evolutionary mechanisms, and information on relevant sources of biological data is essential. The purpose of this review article is to provide a thorough overview about these aspects. Protein domains are basic units defining protein interactions, and the uniqueness of viral domain repertoires, their mode of evolution, and their roles during viral infection make viruses interesting models of study. Mutations at protein interfaces can reduce or increase their binding affinities by changing protein electrostatics and structural properties. During the course of a viral infection, both pathogen and cellular proteins are constantly competing for binding partners. Endogenous interfaces mediating intraspecific interactions-viral-viral or host-host interactions-are constantly targeted and inhibited by exogenous interfaces mediating viral-host interactions. From a biomedical perspective, blocking such interactions is the main mechanism underlying antiviral therapies. Some proteins are able to bind multiple partners, and their modes of interaction define how fast these "hub proteins" evolve. "Party hubs" have multiple interfaces; they establish simultaneous/stable (domain-domain) interactions, and tend to evolve slowly. On the other hand, "date hubs" have few interfaces; they establish transient/weak (domain-motif) interactions by means of short linear peptides (15 or fewer residues), and can evolve faster. Viral infections are mediated by several protein-protein interactions (PPIs), which can be represented as networks (protein interaction networks, PINs), with proteins being depicted as nodes, and their interactions as edges. It has been suggested that viral proteins tend to establish interactions with more central and highly connected host proteins. In an evolutionary arms race, viral and host proteins are constantly changing their interface residues, either to evade or to optimize their binding capabilities. Apart from gaining and losing interactions via rewiring mechanisms, virus-host PINs also evolve via gene duplication (paralogy); conservation (orthology); horizontal gene transfer (HGT) (xenology); and molecular mimicry (convergence). The last sections of this review focus on PPI experimental approaches and their limitations, and provide an overview of sources of biomolecular data for studying virus-host protein interactions.