Insights into monkeypox pathophysiology, global prevalence, clinical manifestation and treatments

Abstract

On 23rd July 2022, the World Health Organization (WHO) recognized the ongoing monkeypox outbreak as a public medical crisis. Monkeypox virus (MPV), the etiological agent of monkeypox, is a zoonotic, linear, double-stranded DNA virus. In 1970, the Democratic Republic of the Congo reported the first case of MPV infection. Human-to-human transmission can happen through sexual contact, inhaled droplets, or skin-to-skin contact. Once inoculated, the viruses multiply rapidly and spread into the bloodstream to cause viremia, which then affect multiple organs, including the skin, gastrointestinal tract, genitals, lungs, and liver. By September 9, 2022, more than 57,000 cases had been reported in 103 locations, especially in Europe and the United States. Infected patients are characterized by physical symptoms such as red rash, fatigue, backache, muscle aches, headache, and fever. A variety of medical strategies are available for orthopoxviruses, including monkeypox. Monkeypox prevention following the smallpox vaccine has shown up to 85% efficacy, and several antiviral drugs, such as Cidofovir and Brincidofovir, may slow the viral spread. In this article, we review the origin, pathophysiology, global epidemiology, clinical manifestation, and possible treatments of MPV to prevent the propagation of the virus and provide cues to generate specific drugs.

Keywords: clinical manifestation; global prevalence; monkeypox virus (MPV); origin; pathophysiology; treatment.

Figure 1

MPV transmission. Zoonotic dissemination of MPV. Animal hosts mainly include rodents (African rope squirrels, prairie dogs, hamsters, and rats) and primates (cynomolgus, rhesus, and gorillas). MPV is an enveloped dsDNA virus belonging to the Poxviridae family, and smallpox is also one of the most prevalent viruses in this family. Wildlife trafficking, habitat degradation, and climate change contribute to the transmission of MPV from new species to other species and increase the bond between people and animals. In the case of wildlife trafficking and illegal hunting, animals are caught, trapped, transported, and sold as food, medicine, and pets. Wildlife trade markets promote disease dissemination, making it possible for viruses from many neighboring species to jump the species barrier. Animal-to-human transmission is mediated by bites, scratches, and slaughtering. Human-to-human transmission occurs through close contact with infected people, such as through respiratory droplets and skin contact, especially MSM. The virus can remain on fomites, such as bedding, linen, and clothes.

Figure 2

MPV life cycle in susceptible host cells. There are two forms of the virus, enveloped virion (EV) and mature virion (MV), which enter the host cell by fusion and micropinocytosis, respectively. MPV genomic structure and compositions are linear double-stranded DNA with nearly 190 kilobase pairs and contained more than 190 open reading frames (ORFs). 5′- and 3′- ends of the genome were inverted terminal repetitions, which formed hairpin-like structures. Double-stranded DNA is released and partially translated into early proteins that are processed into polymerases and immune modulators, while the others undergo replication in the cytoplasm. The resultant DNA partially transcripts into RNA, and the other part translates into intermediate proteins that are transformed into late transcription factors. Viral proteins translated from cytoplasmic RNA together with replicated DNA are assembled into nucleocapsid proteins and then processed into MVs and EVs, which are transported to the cell membrane for exocytosis. UTR, untranslated region.

Figure 3

Accumulated cases of MPV from 1970 to 2020. The disease spread within 15 countries, with the Democratic Republic of the Congo being the worst hit area by the epidemic, followed by Nigeria.

Figure 4

Current cases of MPVX from 1 Jan. to 9 Sep. 2022. More than 57,000 human cases spread globally in more than 100 locations. The United States of America was the worst-hit area, with 2,1893 cases.

Figure 5

Pathophysiology and clinical manifestation of systemic MPV infection. Infection initiates in the upper respiratory tract and progresses to lymph, and then the virus enters the bloodstream through lymphocytes. The MPV in the blood spreads through the circulatory system to all parts of the body, enters the cell through endocytosis, releases DNA, and uses the substances in the cell to transcribe proteins, finally affecting the normal physiological function of the cell. MPV causes lymphocytosis and leukocytosis, thrombocytopenia, elevated aminotransferase levels, and decreased blood urea nitrogen levels. At the same time, symptoms such as multiorgan inflammation and cough and fever also occur.