Inefficient tissue immune response against MPXV in an immunocompromised mpox patient

TY - JOUR

T1 - Inefficient tissue immune response against MPXV in an immunocompromised mpox patient

AU - Matschke, Jakob

AU - Hartmann, Kristin

AU - Pfefferle, Susanne

AU - Wang, Yue

AU - Valdes, Pablo A

AU - Thies, Edda

AU - Schweizer, Michaela

AU - Lütgehetmann, Marc

AU - Schmiedel, Stefan

AU - Bernreuther, Christian

AU - Boyden, Edward S

AU - Glatzel, Markus

AU - Krasemann, Susanne

N1 - © 2024 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.

PY - 2024/7

Y1 - 2024/7

N2 - The recent outbreak of monkeypox virus (MPXV) was unprecedented in its size and distribution. Those living with uncontrolled HIV and low CD4 T cell counts might develop a fulminant clinical mpox course with increased mortality, secondary infections, and necrotizing lesions. Fatal cases display a high and widespread MPXV tissue burden. The underlying pathomechanisms are not fully understood. We report here the pathological findings of an MPXV-driven abscess in gastrocnemius muscle requiring surgery in an immunocompromised patient with severe mpox. Presence of virus particles and infectivity were confirmed by electron microscopy, expansion microscopy, and virus culture, respectively. MPXV tissue distribution by immunohistochemistry (IHC) showed a necrotic core with infection of different cell types. In contrast, at the lesion rim fibroblasts were mainly infected. Immune cells were almost absent in the necrotic core, but were abundant at the infection rim and predominantly macrophages. Further, we detected high amounts of alternatively activated GPNMB+-macrophages at the lesion border. Of note, macrophages only rarely colocalized with virus-infected cells. Insufficient clearance of infected cells and infection of lesion-associated fibroblasts sustained by the abundance of profibrotic macrophages might lead to the coalescing of lesions and the severe and persistent clinical mpox course observed in immunocompromised patients.

AB - The recent outbreak of monkeypox virus (MPXV) was unprecedented in its size and distribution. Those living with uncontrolled HIV and low CD4 T cell counts might develop a fulminant clinical mpox course with increased mortality, secondary infections, and necrotizing lesions. Fatal cases display a high and widespread MPXV tissue burden. The underlying pathomechanisms are not fully understood. We report here the pathological findings of an MPXV-driven abscess in gastrocnemius muscle requiring surgery in an immunocompromised patient with severe mpox. Presence of virus particles and infectivity were confirmed by electron microscopy, expansion microscopy, and virus culture, respectively. MPXV tissue distribution by immunohistochemistry (IHC) showed a necrotic core with infection of different cell types. In contrast, at the lesion rim fibroblasts were mainly infected. Immune cells were almost absent in the necrotic core, but were abundant at the infection rim and predominantly macrophages. Further, we detected high amounts of alternatively activated GPNMB+-macrophages at the lesion border. Of note, macrophages only rarely colocalized with virus-infected cells. Insufficient clearance of infected cells and infection of lesion-associated fibroblasts sustained by the abundance of profibrotic macrophages might lead to the coalescing of lesions and the severe and persistent clinical mpox course observed in immunocompromised patients.

KW - Humans

KW - Immunocompromised Host

KW - Muscle, Skeletal/virology

KW - Mpox (monkeypox)/virology

KW - Monkeypox virus/immunology

KW - Male

KW - Macrophages/immunology

KW - Fibroblasts/virology

KW - Immunohistochemistry

KW - Abscess/immunology

KW - Middle Aged

U2 - 10.1002/jmv.29811

DO - 10.1002/jmv.29811

M3 - Short publication

C2 - 39011825

VL - 96

SP - e29811

JO - J MED VIROL

JF - J MED VIROL

SN - 0146-6615

IS - 7

ER -