Characterization of the cytopathic effect of monkeypox virus isolated from clinical specimens and differentiation from common viral exanthems

While the practice of viral culture has largely been replaced by nucleic acid amplification tests, circumstances still exist in which the availability of viral culture will allow for the diagnosis of infections not included in a provider’s differential diagnosis. Here, we examine the cytopathic effect (CPE) and clinical data associated with eighteen cases of monkeypox virus (MPXV) isolated from nineteen clinical samples submitted for viral culture. During the study period a total of 3,468 viral cultures were performed with herpes simplex virus most commonly isolated (646/3,468; 18.6%), followed by monkeypox virus (19/3,468; 0.6%) and varicella zoster virus (12/3,468; 0.4%). Most MPXV-positive samples were obtained from males (14/19) and taken from genital (7/19) or rectal lesions (5/19). Cycle threshold values of tested samples ranged from 15.3 to 29.0. Growth of MPXV in cell culture was rapid, yielding detectable CPE at a median of 2 days (range: 1-4) often with >50% of the monolayer affected in RMK, BGM, A549, and MRC-5 cell lines. As clinical features of MPXV, HSV, and VZV lesions may overlap, CPE patterns were comparted between viruses. HSV CPE developed in a similar time frame (median: 2 days, range: 1-7) but was more often negative in RMK cells relative to MPXV. VZV grew more slowly (median: 9 days, range: 5-11) and demonstrated CPE affecting ≤25% of cell monolayers when positive. Viral culture remains an important tool for the detection of rare or emerging viral pathogens, particularly when high viral load specimens are easily obtained.