Monkeypox Virus Infection

Monkeypox virus also designated as MPV, MPXV, or hMPXV is a zoonotic Orthopoxvirus that belongs to the family Poxviridae, and causes disease in humans similar to smallpox, although with notably lower mortality. This virus is endemic to western and central Africa, but the 2022 outbreak is mostly being noted in European countries and the Western Hemisphere associated with the exotic pet trade and international travel. Monkeypox virus is one of the human orthopoxviruses along with variola (VARV), cowpox (CPX), and vaccinia (VACV) viruses. The true origin of monkeypox is still unknown but several rodents and small mammals are considered possible sources of the virus. It was named monkeypox because it was first identified in 1958 in macaque monkeys. There are two genetic clades of the monkeypox virus: the West African clade and the Congo Basin clade. The Congo Basin (Central African) clade is reported more frequently and contains examples of documented human-to-human transmission (Ref.1 and 2). The virus can spread from animal to human and from human to human. MPV can enter its host through the oropharynx, nasopharynx, or intradermal routes. The transmission of the virus can occur via salivary or respiratory droplets or contact with mucocutaneous lesions and infectious skin (Ref.3).

MPVs are oval or brick-shaped, slightly pleomorphic, and consist of four major elements—core, lateral bodies, outer membrane, and the outer lipoprotein envelope. The genome is a large (197 kbp) single linear molecule of dsDNA that consists of a dumbbell-shaped core with lateral bodies. The life cycle of the monkeypox virus occurs in the cytoplasm of the host cell. MPV gets attached to the cell and then enters it via fusion or macropinocytosis. The entries of the virus depends on its infectious forms—mature virion (MV) which has a single outer membrane, or extracellular enveloped virion (EV) that contains an additional membrane with a different protein composition. In the EV form, the virus attaches to the host cell membrane which leads to the removal of the EV-specific membrane exposing the underlying MV membrane that fuses with the cell (Ref.3 and 4).

The mature virion uncoats during entry into the cell and after reaching the cytoplasm, the virus releases prepackaged proteins and other factors that stimulate early gene expression. This further leads to early mRNA synthesis followed by early protein formation. Several proteins are required for viral DNA replication, transcription, and translation. Early mRNA and protein synthesis cause the second uncoating process and production of intermediate transcription factors and DNA and RNA polymerases. Subsequently, intermediate mRNA is formed followed by intermediate protein formation that induces the late mRNA expression. mRNA once formed undergoes translation to form structural and non-structural proteins. The DNAs formed during replication and the proteins assemble together to form immature virions that develop into intracellular mature virions (IMVs). IMVs are then released by exocytosis. Some IMVs acquire a second membrane to become intracellular enveloped virions (IEVs). They migrate to the membrane forming cell-associated virions (CEVs) that leave the cell with the help of actin polymerization and filament formation. The CEVs after leaving the cell become extracellular enveloped virions (EEVs). The pathogenesis of the monkeypox virus depends on both its intracellular as well as extracellular forms. The intracellular virions (IMV and IEV) and CEVs help in the spread of the virus from one cell to another or one organism to another whereas the extracellular virions EEVs are responsible for the spread within the infected host (Ref.5 and 6).

The incubation period of the monkeypox disease ranges from 5 to 21 days and the symptoms may vary from 2 to 5 weeks. Monkeypox virus in general doesn't show many mutations but the 2022 variant seems to have more mutations. About 40 mutations have been identified in the 2022 isolates till now. Currently, there is no specific therapy for monkeypox infection; however supportive treatments can be used to provide symptom relief. Antivirals developed for use in smallpox may help in some cases and medications such as tecovirimat can be used in severe cases. Due to poorly available resources in the endemic areas, the diagnosis, clinical recognition, and prevention of monkeypox remain a big challenge (Ref.7).

References:

1. Monkeypox virus emerges from the shadow of its more infamous cousin: family biology matters.

Xiang Y, White A.
Emerg Microbes Infect. 2022 Dec;11(1):1768-1777. doi: 10.1080/22221751.2022.2095309.

2. The changing epidemiology of human monkeypox-A potential threat? A systematic review.

Bunge EM, Hoet B, Chen L, Lienert F, Weidenthaler H, Baer LR, Steffen R.
PLoS Negl Trop Dis. 2022 Feb 11;16(2):e0010141. doi: 10.1371/journal.pntd.0010141.

3. The 2022 outbreak and the pathobiology of the monkeypox virus.

Kumar N, Acharya A, Gendelman HE, Byrareddy SN.
J Autoimmun. 2022 Jul;131:102855. doi: 10.1016/j.jaut.2022.102855. Epub 2022 Jun 25.

4. Monkeypox: A Comprehensive Review of Transmission, Pathogenesis, and Manifestation.

Kaler J, Hussain A, Flores G, Kheiri S, Desrosiers D.
Cureus. 2022 Jul 3;14(7):e26531. doi: 10.7759/cureus.26531.

5. Monkeypox: A New Threat?

Kmiec D, Kirchhoff F.
Int J Mol Sci. 2022 Jul 17;23(14):7866. doi: 10.3390/ijms23147866.

6. Monkeypox virus: a re-emergent threat to humans.

Gong Q, Wang C, Chuai X, Chiu S.
Virol Sin. 2022 Jul 9:S1995-820X(22)00120-1. doi: 10.1016/j.virs.2022.07.006. Epub ahead of print.

7. Prevention and Treatment of Monkeypox.

Rizk JG, Lippi G, Henry BM, Forthal DN, Rizk Y.
Drugs. 2022 Jun;82(9):957-963. doi: 10.1007/s40265-022-01742-y. Epub 2022 Jun 28.