Don’t panic when monkeypox comes. Only by knowing “pox” can you fight “pox”!

Monkeypox is a zoonotic viral disease caused by infection with the monkeypox virus (MPXV). Monkeypox is a self-limiting disease for healthy organisms, and its main clinical manifestations include fever, rash, swollen lymph nodes, back pain, muscle pain, etc. [1]. In 1958, MPXV was first isolated from lesions of crab-eating macaques in Copenhagen. It was not until 1970 that the first case of human infection with MPXV was reported. In the early stage of the monkeypox epidemic, it was mainly prevalent in Central Africa and West Africa. However, since May 2022, several non-endemic countries have reported cases of human infection with monkeypox virus [2]. Due to the rapid spread of the monkeypox epidemic, the World Health Organization (WHO) has twice declared the monkeypox epidemic an international public health emergency [3]. MPXV genome sequencing has confirmed the existence of two different MPXV branches, namely the Central African (clade I) and West African (clade II) branches, with case fatality rates of 10.6% and 3.6%, respectively [4]. To date, all human smallpox cases reported outside of Africa have been caused by MPXV clades IIa and IIb.

Schematic diagram of MPXV development history[2]

MPXV is an enveloped DNA virus belonging to the Poxviridae family and the Orthopoxvirus genus. Other viruses of the same genus include Variola Virus (VARV), Vaccinia Virus (VACV) and Cowpox Virus (CPXV) [2]. Monkeypox virus particles produced by host cells mainly have two forms: mature virions (MV) and enveloped virions (EEV) [4]. Viruses are oval in shape under an electron microscope, with a size of approximately 200 x 250 nm. Their structure consists of an outer membrane, surface tubules, two lateral bodies and a dumbbell-shaped nucleoprotein core containing a large double-stranded linear DNA genome [5].

MPXV virus particle structure and electron microscopy diagram [6,8]

How Monkeypox Virus is Transmitted

Monkeypox is a zoonotic disease, but the animal host of MPXV is still unknown. Currently, various rodent species from the rainforests of Central and West Africa, including squirrels and Gambian kangaroos, are considered to be the cause of transmission of the disease [6]. Studies have shown that humans can be infected with MPXV mainly in the following two ways, but the receptors that MPXV uses to invade human host cells are still unknown.

Animal-to-human: Humans can be infected through direct contact with the mucous membranes, body fluids, or tissues of infected animals or by eating undercooked meat, or through scratches or bites from infected animals[7].

Human-to-human: First, humans can be infected through direct contact with respiratory droplets and body fluids of infected people. Second, humans can be infected through sexual transmission. Most cases of monkeypox have been reported in men who have sex with men [8]. Third, MPXV can also be transmitted vertically to the fetus through the placenta.

Schematic diagram of MPXV transmission pathways[8]

Monkeypox virus genome

Schematic diagram of MPXV gene organization structure[9]

The MPXV genome consists of a linear double-stranded DNA of approximately 197 kb in length, encoding approximately 180 proteins. The middle of the MPXV genome is a conserved region that has more than 90% sequence homology with other orthopoxviruses[9], so people who have been vaccinated with smallpox have a certain degree of cross-protection against MPXV[10]. The two ends are terminal inverted repeat sequences, also known as variable regions. Species-specific differences between poxviruses are mainly found in the left and right terminal regions[11]. Since MPXV replicates in the cytoplasm of the host cell, all proteases that catalyze replication, transcription, assembly, and release are encoded by the viral genome.

Summarize

At present, monkeypox outbreaks have occurred in many parts of the world and have been declared an international public health emergency by the WHO. In order to prevent the spread of monkeypox worldwide, my country is also actively developing preventive vaccines and therapeutic drugs for MPXV. In order to prevent infection with MPXV, we should avoid contact with rodents and primates that may be infected with the virus. In addition, we should avoid intimate behavior with people whose health status is unknown.

References:

[1]Mukherjee AG, Wanjari UR, Kannampuzha S, et al. The pathophysiological and immunological background of the monkeypox virus infection: An update[J]. J Med Virol. 2023, 95(1):e28206.

[2]Moss B. Understanding the biology of monkeypox virus to prevent future outbreaks[J]. Nat Microbiol. 2024, 9(6):1408-1416.

[3]Lim CK, Roberts J, Moso M, et al. Mpox diagnostics: Review of current and emerging technologies[J] JMed Virol. 2023, 95(2):e28581.

[4]Tang H, Zhang A. Human mpox: Biology, epidemiology, therapeutic options, and development of small molecule inhibitors[J]. Med Res Rev. 2023, 43(4):1019-1037.

[5]Rampogu S, Kim Y, Kim SW, et al. An overview on monkeypox virus: Pathogenesis, transmission, host interaction and therapeutics[J]. Front Cell Infect Microbiol. 2023,13:1076251.

[6]Gessain A, Nakoune E, Yazdanpanah Y. Monkeypox[J]. N Engl J Med. 2022,387(19):1783-1793.

[7]Lu J, Xing H, Wang C, et al. Mpox (formerly monkeypox): pathogenesis, prevention, and treatment[J]. Signal Transduct Target Ther. 2023,8(1):458.

[8]Sun Y, Nie W, Tian D, etal. Human monkeypox virus: Epidemiologic review and research progress diagnosis and treatment[J]. J Clin Virol. 2024,171:105662.

[9]Karagoz A, Tombuloglu H, Alsaeed M, et al. Monkeypox (mpox) virus: Classification, origin, transmission, genome organization, antiviral drugs, and molecular diagnosis[J]. J Infect Public Health. 2023,16(4):531-541.

[10]Hong Y, Huang B, Zhang J, et al. Molecular architecture of monkeypox mature virus[J]. Cell Discov. 2024,10(1):108.

[11]Hatmal MM, Al-HatamlehMAI, Olaimat AN, et al. Comprehensive literature review of monkeypox[J]. Emerg Microbes Infect. 2022,11(1):2600-2631.

Source: Shanghai Medical Pathogen Museum