Bioinformatic analysis of monkeypox virus-host cell interactions

Bioinformatic analysis of monkeypox virus-host cell interactions

Although monkeypox virus infection has been predominantly found in West and Central Africa, this double-stranded DNA virus has been reported in many countries outside Africa as of May 2022. Similar to the smallpox virus, the monkeypox virus also belongs to the orthopoxvirus family and is less serious. The World Health Organization recently declared the global monkeypox outbreak a public health emergency of international concern.

Learn: A bioinformatics approach to systematically analyze the molecular patterns of monkeypox virus-host cell interactions. Image credit: Spotted Yeti / Shutterstock

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Typically, symptoms of monkeypox disease last about 2-4 weeks, with a low mortality rate of 3.6% in West Africa and 10.6% in the Congo Basin. The incubation period of this virus is between 5 and 21 days, which is not contagious. Patients infected with monkeypox experience headaches, fatigue, fever, muscle soreness, and lymphadenopathy. Within three days of infection, skin rashes appear on various parts of the body such as the face, hands, legs, oral mucosa, conjunctiva, genitals and cornea.

Two main routes for disease transmission are animal-to-human and human-to-human transmission. Recent studies related to the monkeypox outbreak have reported transmission by MSM (men who have sex with men).

The majority of available data based on monkeypox disease infection are case reports. There are very few studies on the interactions between the virus and the host. It is important to understand the underlying mechanisms associated with monkeypox interactions with humans to cause serious infections. This information could help develop effective treatments to cure and prevent monkeypox infections.

A recently published study on the bioRxiv * Preprint server reported the interaction between monkeypox and human cells. Molecular sequences were screened to identify differentially expressed genes (DEGs) and their associated signaling, expression regulation, and metabolic pathways. These results may help determine an effective target for future treatment of monkeypox disease.

About studying

To evaluate the effects of monkeypox infection on human cells at the transcript level, molecular sequencing datasets, namely GSE36854 and GSE11234, were obtained from the Gene Expression Omnibus (GEO) database. The GSE36854 data set contained eight samples of vaccinia virus strain IHD-W, vaccinia virus strain Brighton Red, monkeypox virus strain MSF infected with Hela cells, and one blank sample.

The GSE11234 dataset was based on GPL6763, which included many types of poxvirus and human genome template information. The monkeypox-infected Hela cell samples were analyzed to observe genomic changes. The molecular sequences were processed and visualized to identify significantly uniquely expressed genes

Study results

A total of 84 DEGs other than histone genes were found, which were used for further studies. Viral interactions rely heavily on early genes to infect host cells and ensure their survival, replication and transmission. These genes are also associated with the regulation of host immunity. Therefore, the gene expression status of monkeypox virus was analyzed and 26 putative early genes encoding the ankyrin repeat protein were discovered.

When comparing sequencing data from many monkeypox samples from the 2022 epidemic and the D1L gene documented from the UK in 2018, several site mutations were observed. These mutations could be responsible for better adaptation in the human host and improved human-to-human transmission.

The changes inside the body caused by external stimuli could be examined by analyzing signaling pathways. DEGs from monkeypox-infected Hela cells were observed to be associated with KEGG signaling pathways, such as TNF signaling pathway, IL-17 signaling pathway, NF-kappa B signaling pathway, cytokine-cytokine receptor interaction, C-type lectin receptor signaling pathway, Kaposi's sarcoma-associated herpesvirus infection, Th17 cell differentiation, NOD-like receptor signaling pathway, small cell lung cancer and human T-cell leukemia virus infection. This finding suggests that monkeypox infection triggers immune responses and causes an inflammatory response.

Genetic disease analysis (GD) was performed to predict the relationship between monkeypox DEGs and various diseases. This analysis revealed the association of monkeypox infection with liver cirrhosis, reperfusion injury, mammary neoplasms, inflammation, hypertensive disease, juvenile arthritis, and brain ischemia. The results of this study were consistent with previous reports revealing complications and sequelae of monkeypox. In addition, the current study also observed an association between monkeypox infection and the manifestation of schizophrenia and psychological depression.

The role of prostaglandin endoperoxide synthase 2 (PTGS2), also known as cyclooxygenase 2 (COX-2), has not been reported in monkeypox infection. However, based on available evidence related to other diseases, monkeypox virus was thought to regulate the pathological process by controlling PTGS2.

The hub genes such as IFIT1, IFIT2, IER3, ZC3H12A, IL11, EREG, IER2, FST, NFKBIE and AREG from monkeypox-infected HELA cells were extracted. Typically, hub genes are associated with various biological processes. The authors identified the main transcription factors that regulate hub genes, i.e. h. IRF1, GLIS2, SIN3A, FOXJ2, Smad5, ZFX and ATF1, as well as miRNAs (e.g. hsa-mir-21-3p, hsa-mir-16-5p, hsa-mir -520c-3p, hsa-mir -1343-3p, hsa-mir-335-5p and hsa-mir -203-3p).

Conclusions

The current study found that monkeypox virus inhibits two antiviral genes, namely IFIT1 and IFIT2. In addition, bioinformatics analysis through the CellMiner database showed that AP-26113 (brigatinib) and itraconazole are promising for the treatment of monkeypox infections.

*Important NOTE

bioRxiv publishes preliminary scientific reports that have not been peer-reviewed and therefore should not be considered conclusive, guide clinical practice/health behavior, or be treated as established information.

Reference:

• Tang, Z. et al. (2022) Ein bioinformatischer Ansatz zur systematischen Analyse der molekularen Muster von Interaktionen zwischen Affenpockenvirus und Wirtszelle. bioRxiv 2022.10.12.511850; doi: https://doi.org/10.1101/2022.10.12.511850, https://www.biorxiv.org/content/10.1101/2022.10.12.511850v1

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