A review of Mpox: Biological characteristics, epidemiology, clinical features, diagnosis, treatment, and prevention strategies

Abstract

The outbreak of monkeypox virus (MPXV) was declared a Public Health Emergency of International Concern (PHEIC) by the World Health Organization (WHO), and the zoonotic disease caused by viral infection was renamed as "Mpox" on November 28, 2022. Currently, there is no approved vaccine or specific antiviral treatment for Mpox, and a main preventive strategy against MPXV infection remains the smallpox vaccine. Although there was an emergency use authorization (EUA) of Brincidofovir and Tecovirimat for the clinical treatment of clade II Mpox, while Tecovirimat failed to reduce the duration of Mpox lesions among patients infected with clade I Mpox in the Democratic Republic of the Congo (DRC). Therefore, it is still an urgent need to develop an effective medication. This review aims to enhance the understanding of Mpox and contribute to its prevention and treatment strategies, it provides a systemic introduction of the biological and epidemiological characteristics of MPXV, the clinical feature and diagnosis of Mpox, as well as treatment and prevention strategies, which will improve the comprehension about MPXV and offer potential strategies for clinical treatment.

Keywords: MPXV; Mpox; Orthopoxvirus; monkeypox; viral outbreak.

FIGURE 1

Biological characteristics of MPXV. (A) Genome structure of MPXV. The genome of MPXV is a large double‐stranded DNA structure of 197 kb length. The highly conserved central region is located at genomic nucleotide positions 56,000—120,000 and is flanked by variable ends that include inverted terminal repeats (ITR), comprising of a set of short tandem repeats and terminal hairpins. There are 190 non‐overlapping ORFs on the genome, four of which are located in reverse variable terminal repeat sequences. (B) Life cycle of MPXV. Mature virus (MV) attaches to the cell surface via interactions between viral ligands and supracellular receptors. And subsequently enters the cell either under neutral conditions via cell membrane fusion, or via an endosomal uptake pathway mediated by actin and a low pH, a pattern similar to the macrophage drinking mechanism. Enveloped viruses (EVs) remove the extra membrane envelope (becomes to MVs) prior to entry, and enter the cell in the same manner. After entering the host cytoplasm, the viral particles undergo three stages of gene expression, namely early, intermediate, and late stages. In the beginning, the virus initiates early transcription, and early proteins such as growth factors and transcription factors are expressed. Subsequently, DNA replication which is inhibited by Cidofovir and Brincidofovir happens, followed by intermediate/late transcription and expression. And the genomic DNA and late proteins are assembled to pre‐mature virion in the “cytoplasmic virus factory,” with morphogenesis changes, intracellular mature virus particles (IMVs) are formed. And IMV can be wrapped by the additional envelope to form intracellular enveloped virus particles (IEVs), specifically, the wrapping could be hindered by Tecovirimat. IEVs can be released from the cell by forming an actin tail to obtain extracellular enveloped virus particles (EEV), whereas IMV can only be released from the cell upon cell lysis. Currently, no treatment for MPXV infections has been approved. And United States Strategic National Stockpile (SNS) recommends clinicians to consider Tecovirimat, Brincidofovir, and Cidofovir (developed for use in patients with smallpox) as the options for the treatment of Mpox.

FIGURE 2

Symptoms of Mpox, immuno‐mechanisms, and treatment targets of MPXV. After the incubation period of MPXV, except for skin rashes on the head, face, trunk, limbs, nail bed, anus, and genitals, patients generally have symptoms such as fever, cough, sore throat, fatigue, muscle pain, headache, swollen lymph nodes, etc. A few patients experience symptoms such as nausea, vomiting, and diarrhea due to proctitis. Typical features of systemic viral invasion include swollen lymph nodes in the neck, armpits, and groins. Three types of immune defense mechanisms are involved in MPXV infection, namely antigen‐antibody binding (e.g., JYNNEOS vaccine), host interferon response, and interferon‐mediated signaling pathway. IL‐15 therapy can induce the production of NK and CD8⁺ cells, and increased NK cell counts prevent fatal MPXV infection. MPXV activates IFN‐1 secretion in almost all cell types, and IFN‐1 activates the JAK/STAT pathway in an antiviral state. The drug targets of MPXV are summarized on the right side. The targets of MPXV inhibition and related drugs were as followed.

FIGURE 3

Global epidemic distribution of human Mpox cases from 1958 to September 30, 2023. (A) The timeline of monkeypox infection. (B) The top ten countries with confirmed cases of human Mpox in the world are the USA (n = 30,636), Brazil (n = 10,967), Spain (n = 7611), France (n = 4158), Colombia (n = 4090), Mexico (n = 4062), Peru (n = 3812), the UK (n = 3805), Germany (n = 3708), and China (n = 1794). Together, these countries account for 81.9% of reported cases globally (the retrieval date is the public data from the WHO, published on October 20, 2023).^{[ 244 ].}

FIGURE 4

The hosts and transmission of MPXV. It is generally accepted that squirrels are the primary hosts of MPXV. Black‐tailed prairie dogs infected with MPXV spilled out of Africa and spread the virus to humans and other animals. Rabbits, monkeys, orangutans, etc., have become animal hosts of MPXV by accident, and until now, it has been difficult to prove that the transmission of MPXV is clearly related to non‐human primates. MPXV can be transmitted through direct contact, respiration, and blood, and increasing evidence suggests that patients can be infected through sexual contact and vertical transmission.

FIGURE 5

Main assays for the diagnosis of Mpox. The primary assays include nucleic acid detection, antigen and antibody detection, and pathological diagnosis. PCR has become a widely used and early tracing technique in diagnosing Mpox. Immunologic diagnosis depends on antigen specificity. Microscopic examination reveals simple pathogenic morphological differences.

FIGURE 6

Vaccine development and immune response pathways for prevention of MPXV. Vaccine development and immune response pathways for MPXV prevention. (A) Immune response pathways for vaccines against MPXV. The virus recognizes the receptor and binds to the receptor; CTL, NK cells, neutrophils, T cells, etc. accumulate around the infected cells and activate the primary immune pathway in the body to inhibit viral replication; macrophages phagocytose the virus and initiate the adaptive immune response, B cells differentiate and proliferate to plasma cells that can produce antibodies, plasma cells secrete a large number of antibody molecules into the blood circulation, antibodies bind to antigens to form antigen complexes, and further inactivate and remove antigens. (B) MPXV vaccines are mainly used to prevent viral infections. Common vaccines include live‐attenuated, inactivated, DNA, RNA, and subunit recombinant protein vaccines.