Monkeypox virus

The monkeypox virus is an enveloped double-stranded DNA virus that causes the zoonotic disease monkeypox characterized by a rash that follows other symptoms, such as fever, headache, swelling of lymph nodes, back pain, myalgia, and lack of energy. Monkeypox, the disease caused by the monkeypox virus, is similar to but milder than the disease smallpox, caused by the variola virus. The monkeypox virus, variola virus, vaccinia virus, and Alaskapox virus belong to the Orthopoxvirus genus within the Poxviridae family and Chordopoxvirinae subfamily. Vaccinia virus, which causes cowpox, was used as a vaccine to irradicate smallpox and is available in attentuated form for humans as a vaccine against orthopox viruses. Similar to other orthopoxviruses, the monkeypox virus is oval or brick-shaped with a lipoprotein-based outer membrane.

The monkeypox virus was named for its initial discovery in monkeys in a laboratory in Denmark in 1958. The first human case of monkeypox occurred in 1970 in a baby in Zaire, now the Democratic Republic of the Congo (DRC). Monkeypox is endemic in the DRC as well as Benin, Cameroon, the Central African Republic, Gabon, Ghana (animals only), Ivory Coast, LIberia, Nigeria, the Republic of the Congo, Sierra Leone, and South Sudan. An outbreak of monkeypox occurred in the US in 2003 that was linked to prairie dogs that were housed with animals imported from Ghana. In May 2022, an unusual monkeypox outbreak began to be reported in non-endemic countries in Europe and North America with no travel links to endemic areas.

The monkeypox virus is transmitted between humans by close contact with lesions, bodily fluids, respiratory droplets, and contaminated materials, such as bedding. Various animal species are susceptible to the monkeypox virus, but the exact reservoir(s) and mechanism by which monkeypox virus maintains circulation are not known.

There were two distinct clades of monkeypox in endemic areas, which are the Central African (or Congo Basin) clade and the West African clade. As of June 2, 2022, only the West African clade of monkeypox had been detected in the atypical monkeypox outbreak of 2022 in non-endemic areas. Since the 2022 monkeypox outbreak, three distinct clades of the monkeypox virus are recognized. Clade 2 and clade 3 fall within the “West African” clade, which causes less severe disease. Clade 1 is formerly known as the “Central African” or “Congo Basin” clade, which is associated with higher fatality. DNA sequences from monkeypox in the 2022 outbreak correspond to clade 3.

The monkeypox virus enters its host by the oropharynx, nasopharynx, or intradermal routes. At the inoculation site, the virus replicates, and then it spreads to regional lymph nodes. Later, the virus spreads to other body organs.

Poxviruses replicate in the cytoplasm, and their DNA encodes proteins for DNA replication and gene expression. The two strands of their linear, double-stranded DNA genome are linked by hairpin ends. The monkeypox virus genome is about 196,858 base pairs and encodes approximately 190 proteins. The virus attaches to the cell surface using viral ligands, which attach to cell surface receptors such as chondroitin sulfate and heparan sulfate. The monkeypox virus may enter the cell by viral fusion or endosomal uptake by a macropinocytosis-like mechanism. Once inside the cell cytoplasm, the monkeypox virus releases viral proteins and enzymatic factors that disable cell defenses and promote expression of early genes, which encode proteins that enable the intermediate stage of viral infection. Intermediate genes are then expressed, which induces the expression of late genes that function mainly as structural proteins, enzymes, and early transcription factors. Viral genomes, enzymes, and transcription factors are assembled into virions enclosed by membrane structures. A characterisitic of poxviruses that is unusual among DNA viruses is they replicate genomic DNA and transcribe genes in the cytoplasm as opposed to inside the nucleus. As with all viruses, the monkeypox virus uses translation machinery, ribosomes, from the host cells for protein synthesis.