Bioinformatic analysis of monkeypox virus host cell interactions

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

The study: A bioinformatics approach to a systematic analysis of molecular patterns of monkeypox virus-host cell interactions.  Image Credit: Dotted Yeti / ShutterstockStady: A bioinformatics approach to a systematic analysis of molecular patterns of monkeypox virus-host cell interactions. Image Credit: Dotted Yeti / Shutterstock

background

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

There are two main ways of transmission of the disease are animal-to-human transmission and human-to-human transmission. Recent studies of monkeypox outbreaks reported transmission through men who have sex with men (Men who have sex with men).

The majority of available data based on the incidence of monkeypox are case reports. Very few studies are available on virus-host interactions. It is essential to understand the underlying mechanisms associated with monkeypox interactions with humans to cause severe infection. This information can help develop effective treatments to cure and prevent monkeypox infection.

A recent study was published in bioRxiv* The prepress server reported the interaction between monkeypox and human cells. Molecular sequences were examined to identify differentially expressed genes (DEGs) and their associated signaling pathway, expression regulation and metabolic pathways. These findings could help identify an effective target for monkeypox treatment in the future.

About the study

To assess the effect of monkeypox infection on human cells at the transcriptional level, the molecular sequencing data sets, namely GSE36854 and GSE11234, were obtained from the Gene Expression Omnibus (GEO) database. The GSE36854 dataset contains eight samples of the IHD-W vaccinia virus strain, the Brighton red vaccinia virus strain, the Monkeypox virus strain infected with Hela cells from MSF, and the blank control.

The GSE11234 dataset was based on GPL6763 which included several types of poxviruses and human genome template information. HeLa cell samples infected with monkeypox were analyzed to observe genomic changes. Molecular sequences were processed and visualized to identify uniquely expressed genes

Results

A total of 84 DEGs were found, excluding histone genes, which were used for further studies. Viral interactions are highly dependent on early genes to infect host cells, ensuring their survival, reproduction 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 suspected early genes, encoding for the ankyrin repeat protein, were detected.

By comparing the sequence data of several monkeypox samples from the 2022 epidemic and the D1L gene documented in 2018 from the United Kingdom, several mutations were observed at the site. These mutations may be responsible for better adaptation in the human host and enhanced human-to-human transmission.

Changes in the internal body due to external stimulus can be studied by analyzing signaling pathways. It was observed that DEGs of monkey pox-infected Hela cells were 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, herpes virus infection Associated with Kaposi’s sarcoma, Th17 cell differentiation, NOD-like receptor signaling pathway, small cell lung cancer, and human T-cell leukemia virus infection. This finding indicates that monkeypox infection elicits immune responses and produces an inflammatory response.

Genetic disease (GD) analysis was performed to predict the relationship between monkeypox DEGs and various diseases. This analysis revealed the association of monkeypox infection with cirrhosis, reperfusion injury, breast tumors, inflammation, hypertensive disease, juvenile arthritis, and cerebral ischemia. The results of this study were consistent with previous reports revealing complications and sequelae of monkeypox. Furthermore, the current study also observed a link between monkeypox infection and manifestations of schizophrenia and mental depression.

The role of prostaglandin-endoperoxide synthase 2 (PTGS2), also known as cyclooxygenase 2 (COX-2), has not been reported in relation to monkeypox infection. However, based on the available evidence regarding other diseases, it has been hypothesized that monkeypox virus regulates the pathological process through the control of PTGS2.

Hub genes, such as IFIT1, IFIT2, IER3, ZC3H12A, IL11, EREG, IER2, FST, NFKBIE, and AREG were extracted from monkey pox-infected HELA cells. Usually, hub genes are associated with different biological processes. The authors identified key transcription factors that regulate axis genes, such as IRF1, GLIS2, SIN3A, FOXJ2, Smad5, ZFX, ATF1, and miRNAs (eg, 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 revealed that monkeypox virus represses two antiviral genes, IFIT1 and IFIT2. In addition, bioinformatics analysis through the CellMiner database indicated that AP-26113 (Brigatinib) and itraconazole show promise for the treatment of monkeypox infection.

*Important note

bioRxiv publishes preliminary scientific reports that are not subject to peer review, and therefore should not be considered conclusive, guide clinical practice/health-related behavior, or be treated as established information.

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