Immunopathogenesis of Orthopoxviridae: insights into immunology from smallpox to monkeypox (mpox)

Abstract

Since 2019, notable global viral outbreaks have occurred necessitating further research and healthcare system investigations. Following the coronavirus disease 2019 (COVID-19) pandemic, in 2022, whilst severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains evolved, monkeypox virus (MPXV) infections became more evident. MPXV is of the Orthopoxviridae genus, belonging to the family Poxviridae. Zoonotic transmission (animal-to-human transmission) may occur. The Orthopoxviridae genus includes other orthopoxviruses (OPXVs) present in animal host reservoirs that include cowpox viruses (CPXVs), vaccinia virus (VACV), and variola virus (VARV), with the latter being a causal agent of smallpox and excessive mortality. This review aims to present facts about MPXV-specific pathogenesis, epidemiology, and immunology alongside historical perspectives. MPXV was rarely reported outside Africa before April 2000. Early research since 1796 contributed towards the eradication of VARV leading to immunisation strategies. The World Health Organisation (WHO) announcement that VARV had been eradicated was confirmed in 1980. On the 23rd of July 2022, the WHO announced MPXV as a health emergency. Therefore, concern due to the propagation of MPXV causing monkeypox (mpox) disease requires clarity. Infected hosts display symptoms like extensive cellular-initiated rashes and lesions. Infection with MPXV makes it difficult to differentiate from other diseases or skin conditions. Antiviral therapeutic drugs were typically prescribed for smallpox and mpox disease; however, the molecular and immunological mechanisms with cellular changes remain of interest. Furthermore, no official authorized treatment exists for mpox disease. Some humans across the globe may be considered at risk. Historically, presenting symptoms of mpox resemble other viral diseases. Symptoms include rashes or lesions like Streptococcus, but also human herpes viruses (HHVs), including Varicella zoster virus (VZV).

Cellular Pathophysiology in Zoonotic Transmission of Orthopoxviruses (OPXVs) from Animal Host to Human

“…Cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and interferons (IFNs) are crucial in the immune response against OPXV infections. IL-1 and TNF-alpha initiate local inflammation and activate endothelial cells to express adhesion molecules, facilitating immune cell recruitment (Brown et al, 2023;. IL-6 amplifies the acute phase response, stimulating hepatocytes to produce acute-phase proteins.…”

“…IL-6 amplifies the acute phase response, stimulating hepatocytes to produce acute-phase proteins. IFNs induce an antiviral state in neighboring cells, inhibiting viral replication and spread (Brown et al, 2023;.…”

“…The following table highlights the similarities and differences in pustular formation among specific OPXVs (Variola, Vaccinia, Cowpox, and Monkeypox). Sources: Brown et al, 2023;Chan et al, 2022;Hatmal et al, 2022; Copyright © 2024 Nicholas A. Kerna, et al All rights reserved.…”

Pan‐microscopic examination of monkeypox virus in trophoblasts cells reveals new insights into virions release through filopodia‐like projections

“…During the latest MPX epidemic, the symptoms described in several report cases highlight the presence of a broad spectrum of cutaneous/ mucosal manifestations, mainly anogenital, but also oropharyngeal involvement, and most infected patients reported prodromal signs/ symptoms (fever, asthenia, and lymphadenopathy) before the rash. [5][6][7] Varying in size from 130 to 450 kb, 8 poxviruses are viruses wrapped with a double-stranded DNA genome. 9 Within the host cell, poxviruses assemble within the cytoplasmic where various virion assembly intermediates such as immature, mature, and extracellular wrapped states are found.…”