![]() ![]() During the prodrome phase (a period prior to the development of a rash), an infected person can experience fever, chills, malaise, headache, backache, sore throat, shortness of breath, and swollen lymph nodes ( 12, 13). After exposure and infection, there is about a 10 to 14 day incubation period, which is then followed by a prodrome period of about two days. Similarly, some human-to-human transmissions are thought to occur through respiratory droplets ( 8). Some cases of human monkeypox that occurred in the US revealed that respiratory transmission from an infected animal to a human was possible ( 11). For example, infections are believed to occur through cuts in the skin while handling or eating infected animals ( 8). The virus is thought to be transmitted to humans through close contact with infected animals. The main animal reservoir for monkeypox has not been conclusively determined, but rodents such as Gambian giant rats and rope squirrels are suspected to be a reservoir ( 7- 10). The first reported case of human monkeypox occurred in 1970 in a child from the Democratic Republic of Congo (DRC), formerly known as Zaire ( 5, 6). The clinical features of monkeypox are very similar to those of smallpox. This review does not focus on the immune responses generated by live vaccinia virus vaccination (which provides cross protection to variola and monkeypox viruses), since this topic was recently reviewed in this journal ( 4). This review focuses on viral immune modulatory proteins that distinguish monkeypox virus from variola and vaccinia viruses. There are also concerns that in the current setting of limited smallpox vaccination, monkeypox could become a more efficient human pathogen. ![]() Because the clinical features of monkeypox closely resemble smallpox, it makes it difficult to clinically distinguish one infection from the other unless specific diagnostic tests are performed. The prospect of the global spread of monkeypox was recently seen with the first cases of monkeypox occurring in the Western Hemisphere due to the accidental importation of infected animals ( 3). Since routine smallpox vaccination ended decades ago, there is growing concern that monkeypox may become the next emerging poxvirus to plague humankind ( 2). With the last naturally occurring case of smallpox in 1977 and the declaration of global eradication of smallpox by the World Health Organization (WHO) in 1980, routine smallpox vaccination around the world ended in the mid-1980s. Vaccinia virus is commonly studied in laboratories as a model poxvirus. The vaccine that helped eradicate smallpox was the closely related vaccinia virus. Variola virus caused smallpox and was ultimately eradicated as a disease through the combination of a successful containment strategy, the fact that there was no animal or environmental viral reservoirs, and the use of a very effective vaccine ( 1). Additional members of this genus include variola virus, vaccinia virus, ectromelia (mousepox) virus, and cowpox virus. ![]() Monkeypox virus is a member of the family Poxviridae, genus Orthopoxvirus. ![]() In the current setting of limited smallpox vaccination and little orthopoxvirus immunity in parts of the world, monkeypox could become a more efficient human pathogen under the right circumstances. Genetic differences likely also explain the differences in virulence between two strains of monkeypox virus found in two different regions of Africa. There are also differences in genes that code for virulence factors and host range proteins. There are differences found in several of these immune-modulating genes including genes that express proteins that affect cytokines such as interleukin-1, tumor necrosis factor, and interferon. In this review, we focus on the viral proteins that are predicted to modulate the host immune response and compare the genome of monkeypox virus with the genomes of variola virus and the vaccinia virus, the orthopoxvirus that represented the smallpox vaccine. The reason for this may lie in the virus' genetic makeup, ecological changes, changes in host behavior, and the fact that with the eradication of variola virus, routine smallpox vaccination is no longer carried out. Although monkeypox virus is less fatal and not as transmissible as variola virus, the causative agent of smallpox, there is concern that monkeypox virus could become a more efficient human pathogen. However, in 2003, there was an outbreak in the US, representing the first documented monkeypox cases in the Western hemisphere. Monkeypox is a disease that is endemic in Central and Western Africa. ![]()
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