Filoviruses Infect Rhesus Macaque Synoviocytes in Vivo and Primary Human Synoviocytes in Vitro

Cooper, Timothy K.; Logue, James; Zlobec, Inti; Perry, Donna L.; Hart, Randy; Hischak, Amanda M.W.; Bernbaum, John G.; Gerhardt, Dawn M.; Rojas, Oscar; Bohannon, J. Kyle; Hagen, Katie R.; Johnson, Reed F.; Crozier, Ian; Jahrling, Peter B.; Hensley, Lisa E.; Bennett, Richard S.

doi:10.1016/j.ajpath.2020.05.013

Cited by 5 publications

(7 citation statements)

References 51 publications

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“…To enable future studies to dissect intricate viral tissue interactions, we next sought to extend our antibody validation to EBOV-specific reagents. We identified three antibodies from previous literature targeting the EBOV structural glycoprotein (GP), viral RNA encapsidation nucleoprotein (NP), and virion assembly protein and interferon antagonist VP40 ( 18 , 19 , 24 ). We first tested these antibodies using IHC on spleen collected from healthy controls and EBOV-infected NHPs ( Figure 5 ).…”

Section: Resultsmentioning

confidence: 99%

“…The initial host antibody marker selection was based on prior knowledge and antibody clones described in previous studies (12)(13)(14)(15)(16)(17)(18)(19). Various factors, such as the time between tissue collection and fixation, duration of fixation, processing into paraffin blocks, and storage conditions can affect tissue integrity and immunohistochemical analysis (20).…”

Section: Host Antibody Validation In Healthy Lymphoid Tissuesmentioning

confidence: 99%

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Rhesus Macaque CODEX Multiplexed Immunohistochemistry Panel for Studying Immune Responses During Ebola Infection

et al. 2021

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Non-human primate (NHP) animal models are an integral part of the drug research and development process. For some biothreat pathogens, animal model challenge studies may offer the only possibility to evaluate medical countermeasure efficacy. A thorough understanding of host immune responses in such NHP models is therefore vital. However, applying antibody-based immune characterization techniques to NHP models requires extensive reagent development for species compatibility. In the case of studies involving high consequence pathogens, further optimization for use of inactivated samples may be required. Here, we describe the first optimized CO-Detection by indEXing (CODEX) multiplexed tissue imaging antibody panel for deep profiling of spatially resolved single-cell immune responses in rhesus macaques. This 21-marker panel is composed of a set of 18 antibodies that stratify major immune cell types along with a set three Ebola virus (EBOV)-specific antibodies. We validated these two sets of markers using immunohistochemistry and CODEX in fully inactivated Formalin-Fixed Paraffin-Embedded (FFPE) tissues from mock and EBOV challenged macaques respectively and provide an efficient framework for orthogonal validation of multiple antibody clones using CODEX multiplexed tissue imaging. We also provide the antibody clones and oligonucleotide tag sequences as a valuable resource for other researchers to recreate this reagent set for future studies of tissue immune responses to EBOV infection and other diseases.

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Section: Resultsmentioning

confidence: 99%

Section: Host Antibody Validation In Healthy Lymphoid Tissuesmentioning

confidence: 99%

Rhesus Macaque CODEX Multiplexed Immunohistochemistry Panel for Studying Immune Responses During Ebola Infection

et al. 2021

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“…Indeed, uveitis and retinitis have been described in NHPs persistently infected with EBOV after surviving the acute phase of disease (50). Additionally, other studies have described viral persistence in immune-privileged sites (e.g., eyes, testes, brain) in NHPs surviving filovirus challenge (51,52), with CD68 + circulating and tissue-resident (e.g., synovial) macrophages being suggested as a possible reservoir for persistent infection (50,51,53). A recent report described a case of fatal apparent recrudescence in a rhesus macaque after treatment with an anti-EBOV mAb cocktail (52).…”

Section: Discussionmentioning

confidence: 99%

Combination therapy with remdesivir and monoclonal antibodies protects nonhuman primates against advanced Sudan virus disease

Cross¹,

Bornholdt²,

Prasad³

et al. 2022

JCI Insight

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“…CD68 + macrophages were also increased in numbers in the interstitium of dorsal root ganglia and autonomic ganglia in EBOV-challenged rhesus macaques compared with controls. The CD68 + cells around dorsal root ganglia neurons were large, plump/ameboid, and had foamy cytoplasm (Liu et al, 2020). Inclusion bodies have been reported in macrophages within ganglia in EBOV-infected guinea pigs (light microscopy only) (Cooper et al, 2018).…”

Section: Nervous Systemmentioning

confidence: 97%

“…Inclusion bodies have been reported in macrophages within ganglia in EBOV-infected guinea pigs (light microscopy only) (Cooper et al, 2018). Inclusion bodies and filamentous EBOV particles were present in macrophages near the neuronal perikaryon in the ganglia of the seminal vesicle and adrenal gland in an EBOV-infected rhesus macaque model (Liu et al, 2020). Lipid-laden macrophages in an axillary/brachial nerve without inclusion bodies were also observed in an EBOVinfected guinea pig model (light microscopy only) (Cooper et al, 2018).…”

Section: Nervous Systemmentioning

confidence: 99%

Macrophage infection, activation, and histopathological findings in ebolavirus infection

Wanninger

Millian²,

Saldarriaga³

et al. 2022

Front. Cell. Infect. Microbiol.

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Macrophages contribute to Ebola virus disease through their susceptibility to direct infection, their multi-faceted response to ebolaviruses, and their association with pathological findings in tissues throughout the body. Viral attachment and entry factors, as well as the more recently described influence of cell polarization, shape macrophage susceptibility to direct infection. Moreover, the study of Toll-like receptor 4 and the RIG-I-like receptor pathway in the macrophage response to ebolaviruses highlight important immune signaling pathways contributing to the breadth of macrophage responses. Lastly, the deep histopathological catalogue of macrophage involvement across numerous tissues during infection has been enriched by descriptions of tissues involved in sequelae following acute infection, including: the eye, joints, and the nervous system. Building upon this knowledge base, future opportunities include characterization of macrophage phenotypes beneficial or deleterious to survival, delineation of the specific roles macrophages play in pathological lesion development in affected tissues, and the creation of macrophage-specific therapeutics enhancing the beneficial activities and reducing the deleterious contributions of macrophages to the outcome of Ebola virus disease.

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Filoviruses Infect Rhesus Macaque Synoviocytes in Vivo and Primary Human Synoviocytes in Vitro

Cited by 5 publications

References 51 publications

Rhesus Macaque CODEX Multiplexed Immunohistochemistry Panel for Studying Immune Responses During Ebola Infection

Rhesus Macaque CODEX Multiplexed Immunohistochemistry Panel for Studying Immune Responses During Ebola Infection

Combination therapy with remdesivir and monoclonal antibodies protects nonhuman primates against advanced Sudan virus disease

Macrophage infection, activation, and histopathological findings in ebolavirus infection

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