A Brief Introduction of Monkeypox

A Brief Introduction of Monkeypox

Recently, monkeypox virus is widespread in west and central Africa, which attracts global attention. The World Health Organization (WHO) states that monkeypox constitutes a "moderate risk" to overall public health at the global level after cases were reported in countries, but it is not ruled out that the risk level may be increased with the spread of the virus in future days. Notably, this is the first time monkeypox virus has spread in multiple "non-endemic countries" outside of Central and West Africa, with human-to-human transmission.

Like smallpox virus and vaccinia virus, monkeypox virus belongs to the Orthopoxvirus genus, and their clinical manifestations are also very similar. Monkeypox and vaccinia are usually mild and most people recover within a few weeks without treatment. Smallpox virus is a extremely contagious disease with a mortality rate of 30%-80%.

Monkeypox virus is one of the largest double-stranded DNA virus. The electron microscope shows rectangular enveloped with a membrane(Fig1). Infected Vero cells depicted typical cytopathic effect, exhibiting cell detachment and rounding.

Fig1. Monkeypox virus under electron microscopy.

In the long-term evolution, monkeypox virus has evolved a set of proteins that act on antiviral signals of target cells against the clearance of host immunogen system, which are called host range factor(Hrf). The genes that encode them are called host range genes (Hrg). Whether monkeypox virus can successfully infect the host depends on the “mutual game” between Hrf and the host immune system. Evidence of

monkeypox virus infection has been found in many animals including rope squirrels, tree squirrels, Gambian pouched rats, dormice, different species of monkeys and others. Its broad host spectrum is also associated with Hrg-encoded proteins. Hrf can regulate different signal transduction pathways of host cells, which leads to better host survival and increased mobility.

Table 1. the Host Range Genes of Monkeypox Virus

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Gene

At present, the research on the infection mechanism of monkeypox virus mainly focuses on two aspects: one is the mechanism of inhibiting the activity of interferon (IFN), and the other is the inhibition of the inflammatory signaling cascade activation system.

Some conservative structures of monkeypox virus can be recognized by the host immune system during infection and replication, such as enveloped glycoprotein and double stranded RNA (dsRNA). The conformation of pattern recognition receptors (PRRs) would be changed if it recognizes and binds the pathogen-associated molecular patterns (PAMPs) in host cells. The activation of PRRs recruits adaptor proteins, such as MyD88 and TRAM, activating transcription factors, such as IRF3 and MAP kinase, and inducing the production of IFN. A large amount of soluble receptor proteins are encoded by Hrg of monkeypox virus, which can bind IFNs. These proteins share high structural similarity with IFNR. For example, decoy receptor of Type I interferons and cytokines produced by Hrg can sequester dsRNA to block the initiation of interferon responses. IFN-γ binding protein (IFN-γBPs) coded by Hrg could combine with IFN-γto form Polymeric complex, which could effectively block IFN-γ-mediated anti-virus response.

Monkeypox virus can also regulate the NF-KB signaling pathway to inhibit the inflammatory signaling cascade activation system. The NF-KB pathway would be regulated by the protein expressed by Hrf, so as to avoid the virus be cleared by the host immune system. The ligand-binding protein produced by monkeypox virus can interfere with the gene expression of cytokines such as TNF, LT-α, and IL-1β. Monkeypox virus can also express protein K1L containing ankyrin repeats (ANKs). K1L can prevent the degradation of IkBα in cells, thereby blocking the activation of NF-KB signaling mediated by TLR2/TLR4 and TLR9.

In conclusion, the host range and infection mechanism of monkeypox virus are closely related to the biological function of Hrf. In view of its wide host range, the genetic recombination of different kinds of viruses, and the high risk of cross species transmission, the research on the infection mechanism of monkeypox virus is very important. Cloud-Clone provides relevant detection reagent products for scientific researchers worldwidely.

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