Monkeypox (hMPXV Infection): A Practical Review

Abstract

Monkeypox, a neglected disease previously confined to Africa, is causing a worldwide outbreak affecting predominantly males who have sex with males, especially those who are infected with HIV. The clinical presentation during the current outbreak differs from endemic cases. Treatment with tecovirimat and other antivirals is available. Immunization may be used as preexposure and postexposure prophylaxis.

Figure 1

VACV is a large, enveloped, brick-shaped DNA virus that exists in three infectious forms: the intracellular mature virus (IMV), the intracellular triple-enveloped virus (IEV). and the extracellular double-enveloped virus (EEV). 1. To enter the cell, the EEV has an entry fusion complex (EFC) on the inner envelope. The outer envelope has proteins that interact with laminin and with the glycosaminoglycans (chondroitin sulfate and heparan sulfate, which facilitate interaction with other proteins, such as beta integrin or MARCO. They in turn allow disarming the outer envelope allowing entry of the virion. 2. The viral core that enters the cytoplasm contains the viral DNA as well as DNA-dependent RNA polymerase that allows for synthesis of RNA without the intervention of the cell nucleus. 3. The host cell ribosomes translate early and late genes from the viral mRNA. The early genes codify proteins that counteract host immune defenses and stimulate the replication of viral DNA. The late genes codify for proteins required for viral assembly. 4. Viral DNA and core proteins are assembled to become the IMV. 5. Between 5% and 10% IMV are wrapped by a Golgi cisterna or late endosome (LE) becoming 3-membrane wrapped virions (IEV). The F13L gene of the vaccinia virus encodes the membrane protein p37, which is pivotal in the fusion of the IMV membranes with the Golgi or LE. Tecovirimat binds specifically to the homologous F13L proteins (p37 and others), preventing the formation of IEV. 6. IEV surfs the actin filaments until the outermost membrane of the virion fuses with the extracellular membrane, releasing the two-membrane EEV into the extracellular.

Figure 2

(A) A baby with “endemic” monkeypox virus in Africa. (B) A male with hMPXV infection following “fisting” (insertion of the hand into the rectum or vagina of someone as a means of sexual stimulation). (C) A female with hMPXV infection after performing cunnilingus and anilingus. Oral lesions not shown.