Monkeypox Biology

With the COVID-19 pandemic still ongoing, another public health threat has the world on alert — a global outbreak of monkeypox virus. As of June 28, 2022, the US has identified 306 cases in 27 states and the District of Columbia, while more than 4,700 cases have been identified in over 40 countries worldwide (CBS). In this blog, we will give a quick overview of the basic biology of the monkeypox virus.

Introduction

Monkeypox is a zoonotic (virus transmitted to humans from animals) disease which results in smallpox-like symptoms in humans. The monkeypox virus belongs to the genus Orthopoxvirus, and family Poxviridae. The Orthopoxvirus genus includes 11 distinct but very closely related species (Table 1). Smallpox, a severe disease that resulted in high mortality rates, was caused by a thr Variola virus member of this family of viruses. Through a successful containment strategy and an effective vaccine and vaccination program, the World Health Organization declared global eradication of smallpox in the mid-1980s. The vaccine that helped eradicate smallpox was the closely related vaccinia virus — a prototype of the family that is commonly studied in laboratories as a model poxvirus. Because routine vaccination for smallpox ended years ago, there is growing concern that monkeypox maybe the next viral pandemic.

Species Animals Infected
Variola Human
Vaccinia Human, cow, pig, buffalo, rabbit, etc.
Cowpox Rodent, cow, human, cat, etc.
Monkeypox Squirrel, monkey, ape, human
Ectromelia Mouse, mole
Camelpox Camel
Taterapox Gerbil
Volepox Vole
Raccoonpox Raccoon
Skunkpox Skunk
Uasin Gishu Horse

Table 1. Eleven viruses included in the Orthopoxvirus genus and animals infected (adopted from https://www.ncbi.nlm.nih.gov/books/NBK230917/)

History

Monkeypox virus was originally discovered in 1958 when an outbreak of a pox-like disease occurred in a monkey colony kept for research in a Danish laboratory. The first human case was recorded in 1970 in a 9-month-old baby boy in the Democratic Republic of the Congo (where it is endemic). Since then, it spread to other regions of west and central Africa. Epidemiological studies revealed two different clades of monkeypox virus — the west African clade with a milder form of disease, and lower rates of fatality and human-to-human transmission — and the central African clade with a more severe form with increased transmissibility. The first monkeypox outbreak outside of Africa was identified in the US in 2003 and was linked to contact with infected pet prairie dogs. However, with the recent outbreak, as of May 2022, multiple cases of monkeypox were identified in several other non-endemic countries.

The virus

Poxviruses are enveloped, brick-shaped, large (240-300 nm) DNA viruses enclosed by a corrugated lipoprotein outer membrane that replicate entirely in the cytoplasm. They have a linear double-stranded genome (130-230 kbps) that encode for approximately 200 proteins — some structural and some non-structural. The common proteins are responsible for cross-reactive immunity which allows for vaccination against disease from another poxvirus of the same genus.

Poxvirus DNA synthesis is detected 2 hours post infection. The first step in the infection cycle is attachment of the virus to the surface of the invading host. For poxviruses, the synthesis of messenger RNA takes place before uncoating and is mediated by RNA polymerase and other enzymes packed within the virion. Early messenger RNA is translated into proteins that uncoat the virus and allow for replication and transcription of a second class of intermediate genes which allow for transcription of a late class of genes that is ultimately translated into structural and enzyme components of the virion. The final phase of the growth cycle is when the virus exits the cell by lysis or more commonly by exocytosis.

Monkeypox Virus

Clinical features of infection

The clinical features of monkeypox closely resemble those of smallpox. After infection, there is a 10–14-day incubation period which is followed by a prodrome period of 2 days. During this prodrome period (before the appearance of a rash), patients may experience fever, chills, malaise, headache, back ache, sore throat, shortness of breath and swollen lymph nodes. A possible distinguishing characteristic of monkeypox from smallpox maybe the enlarged lymph nodes in the submandibular, cervical, and inguinal regions. This feature is seen in about 90% of monkeypox cases. After this prodrome period, a maculopapular rash develops with lesions ranging from 0.2 – 1 cm. This is also the time when the patient is most infectious. The lesions appear in the face, trunk and extremities and can progress through multiple stages from papules, vesicles, pustules, and a final crusting phase where there is scabbing and peeling of skin.

Laboratory diagnosis of monkeypox

The optimal sample type for diagnosing monkeypox are skin lesions as they are known to have the highest quantity of virus. Swabs should include lesion surface and/or exudate, roofs from more than one lesion or lesion crusts. Polymerase chain reaction (PCR) is the preferred laboratory test given its accuracy and sensitivity; however, it cannot be used for diagnoses after the infection has cleared. Therefore, other techniques that rely on the host’s immune response to the virus are being used, including enzyme-linked immunosorbent assays (ELISA) that use subtle antigenic differences between viruses for detection.

Spread, prevention and outlook

It is possible to contract monkeypox if scratched, bitten by, or preparing/eating meat from an infected animal. The virus can spread human-to-human through direct contact with an infectious rash, scabs, or body fluids, touching items that previously contacted infectious individuals or respiratory secretions during intimate contact. Pregnant mothers can pass on the infection through the placenta to the fetus.

The CDC does not recommend widespread vaccination for monkeypox at this time, however frequent hand washing and avoiding close contact with infectious individuals and animals is recommended.

While there are no specific treatments for monkeypox, due to its genetic similarity to smallpox, certain antiviral therapies (tecovirimat) recommended for smallpox maybe given to individuals who experience severe illness.

Browse RayBiotech’s catalogue of Monkeypox Research products including real-time PCR detection kits, recombinant proteins, ELISA assays and protein arrays.

References

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