Genomic and ultrastructural analysis of monkeypox virus in skin lesions and in human/animal infected cells reveals further morphofunctional insights into viral pathogenicity

Abstract

Monkeypox (MPOX) is a zoonotic disease that affects humans and other primates, resulting in a smallpox-like illness. It is caused by monkeypox virus (MPXV), which belongs to the Poxviridae family. Clinically manifested by a range of cutaneous and systemic findings, as well as variable disease severity phenotypes based on the genetic makeup of the virus, the cutaneous niche and respiratory mucosa are the epicenters of MPXV pathogenicity. Herein, we describe the ultrastructural features of MPXV infection in both human cultured cells and cutaneous clinical specimens collected during the 2022-2023 MPOX outbreak in New York City that were revealed through electron microscopy. We observed typical enveloped virions with brick-shaped morphologies that contained surface protrusions, consistent with the classic ultrastructural features of MPXV. In addition, we describe morpho-functional evidence that point to roles of distinct cellular

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

“…The shape of the JEG‐3 cell nuclei was circular, and cells contained abundant glycogen granules (Figure 3A1–A2). Observed MPXV particles were morphologically consistent with the literature, 12–15 possessing the typical oval coffee bean or brick shape containing an external membrane and biconcave core. Mean longest and smallest diameters were 274 ± 35 and 193 ± 31 nm ( n = 48), and 305 ± 25 and 220 ± 24 nm ( n = 14), for oval coffee bean and brick‐shaped particles, respectively.…”

“…The acquisition of additional membrane of the trans‐Golgi cisternae or plasma membrane causes a change in the state of the virion which becomes wrapped and or wrapped extracellular. Current data on virion morphology are due to transmission electronic microscopy 10–15 …”

“…Although electron microscopy has provided a better understanding of the cellular infection mechanisms of MPXV by investigating biopsies from animal 19 or human, 10,12,13 and in vitro cell lines, 14,15 the exact mechanisms by which orthopoxviruses cross the placenta during pregnancy have yet to be characterized 20 . Interestingly, one hypothesis for the vertical transmission of MPXV to the fetus in pregnant women is that MPXV could originate from the vagina or maternal bloodstream to infect placental syncytiotrophoblasts via transcytosis or fusion with the trophoblast membrane 20,21 …”

Mpox (Monkeypox) Virus and Its Co-Infection with HIV, Sexually Transmitted Infections, or Bacterial Superinfections: Double Whammy or a New Prime Culprit?

“…Like other OPXVs, MPXV replicates entirely in the cytoplasm and has similar life cycle steps (Figure 1) [2,[22][23][24][25][26], among which viral DNA replication and intracellular virion wrapping steps are targeted by brincidofovir and tecovirimat, respectively [15] (to be discussed in the next section). By employing electron microscopy, Paniz-Mondolfi et al [27] recently observed typical enveloped virions with brick-shaped morphologies containing surface protrusions in MPXV and abundant melanosomes near viral assembly sites in skin lesions isolated from patients affected by the 2022-2023 outbreak. Of note, there are many outstanding questions that remain unanswered in the MPXV life cycle (Figure 1), for example, the cellular receptor of MPXV and the molecular details of virion morphogenesis and egress.…”