Immunosuppressive therapy alleviates murine cytomegalovirus recurrence by reducing TNF-α post cell transplantation with lethal GVHD

Deng, Jiang; Xiao, Jun; Lv, Liping; Ma, Ping; Song, Xiaoyan; Gao, Bo; Gong, Feng; Zhang, Yanyu; Xu, Jinbo

doi:10.1016/j.antiviral.2016.06.015

Cited by 4 publications

(4 citation statements)

References 46 publications

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“… 78 , 79 Reports suggest that TNF-α inhibitors could mitigate CMV viral load via TNF-α reduction. 80 TNF-α inhibitors might also be effective in treating the underlying disease activity that accompanies inflammation-induced CMV replication in colon tissue. 81 Short-term infliximab treatment (<14w) exerts minimal influence on the risk of latent CMV reactivation.…”

Section: Discussionmentioning

confidence: 99%

Cytomegalovirus Pneumonia in Inflammatory Bowel Disease: Literature Review and Clinical Recommendations

Ren,

Yong,

Wang

et al. 2023

IDR

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The objective was to elucidate the correlation between CMVP and immunosuppressive therapy in IBD patients, we hope this review could expand on the significance of CMV as an opportunistic pathogen and the potential impact on morbidity and mortality in IBD patients. Methods: Records and clinical trajectories linked to CMVP in IBD patients were extracted from the PubMed database, irrespective of language barriers. The reference lists incorporated in these studies were manually inspected. Conclusions were generated using straightforward descriptive analysis. Results: In total, 18 IBD patients, including Crohn's disease (CD, 67%) and Ulcerative Colitis (UC, 33%), affected by CMVP were identified from 17 published articles. A minority of these patients (17%) exhibited active disease, whereas the majority (83%) presented with quiescent disease. Fever (100%) and dyspnea (44%) emerged as the most prevalent clinical symptoms. All the patients had undergone immunosuppressive therapy. A significant proportion, up to 89%, had received thiopurine treatment prior to the CMVP diagnosis. Interestingly, none of the patients were subjected to biological therapy. Half of the patients manifested with Hemophagocytic Lymphohistiocytosis (HLH). Almost all patients (94%) were administered antiviral treatment and a substantial 83% experienced full recovery. Immunosuppressive agents were either tapered or discontinued altogether. A subset of patients, 17%, suffered fatal outcomes. Conclusion: Our findings underscore the need for heightened suspicion of CMVP in IBD patients who exhibit symptoms such as fever and dyspnea. During the COVID-19 pandemic, CMVP should be considered a potential differential diagnosis. It was observed that CMVP primarily transpires during CD remission. Azathioprine emerged as the predominant immunosuppressant linked to CMV reactivation. The prompt application of effective antiviral therapy can substantially enhance patient outcomes. CMV vaccine might serve as a viable prevention strategy.

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Section: Discussionmentioning

confidence: 99%

Cytomegalovirus Pneumonia in Inflammatory Bowel Disease: Literature Review and Clinical Recommendations

Ren,

Yong,

Wang

et al. 2023

IDR

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“…Viral titers were assessed using a modified 50% tissue culture infective dose (TCID 50 ) assay, as previously described [28]. Briefly, MEFs were cultured in a 96-well plate and inoculated with serial dilutions of MCMV or centrifuged supernatant from liver homogenates from infected mice.…”

Section: Methodsmentioning

confidence: 99%

“…For the acute infection group, mice were euthanized on day 5 post-infection; mice in the viral reactivation group were maintained for 25 weeks to establish latency as previously described [33,34]. MCMV recurrence in the viral reactivation group was induced as we previously described [28]: BALB/c recipient mice latently infected with MCMV underwent 700cGy total body irradiation and received an intravenous (IV) injection of 1 × 10 7 bone marrow cells plus 1 × 10 7 spleen cells from C57BL/6 mice (male, Vital River). The surviving recipients were euthanized using CO 2 on day 28 post-transplantation.…”

Section: Methodsmentioning

confidence: 99%

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Manipulation of Viral MicroRNAs as a Potential Antiviral Strategy for the Treatment of Cytomegalovirus Infection

Deng¹,

Xiao

Ma³

et al. 2017

Viruses

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Cytomegalovirus (CMV) infection leads to notable morbidity and mortality in immunosuppressed patients. Current antiviral drugs are effective but seriously limited in their long-term use due to their relatively high toxicity. In the present study, we characterized the expression of murine CMV microRNAs (MCMV miRNAs) both in vitro and in vivo. Although 29 miRNAs were detectable during in vitro infection, only 11 miRNAs (classified as Group 1) were detectable during in vivo infection, and as many as 18 viral miRNAs (classified as Group 2) were less detectable (<50% of animals) in both the liver and lungs. In addition, viral miRNA profiles in the blood revealed unstable and reduced expression. We next explored the in vitro effects of viral miRNAs on MCMV replication. The inhibition of Group 1 viral miRNAs had little effect on virus production, but transfected cells overexpressing miR-m01-3-5p, miR-M23-1-5p, miR-M55-1, and miR-m107-1-5p in Group 2 showed statistically lower viral loads than those transfected with control miRNA (29%, 29%, 39%, and 43%, respectively, versus control). Finally, we performed hydrodynamic injection of viral miRNA agomirs and observed lower levels of MCMV recurrence in the livers of animals overexpressing the miR-m01-3-5p or mcmv-miR-M23-1-5p agomirs compared with those of animals transfected with control agomir, confirming the antiviral effects of viral miRNA manipulation in vivo. Therefore, the manipulation of viral miRNA expression shows great therapeutic potential and represents a novel antiviral strategy for the miRNA-based treatment of cytomegalovirus infection.

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IL‐12/IL‐18‐preactivated donor NK cells enhance GVL effects and mitigate GvHD after allogeneic hematopoietic stem cell transplantation

Song

Liu

et al. 2018

Eur J Immunol

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Adoptive transfer of donor NK cells has the potential of mediating graft-versus-leukemia (GVL) effect while suppressing acute graft-versus-host-disease (aGVHD) during allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, these beneficial effects are limited by the transient function of adoptively transferred NK cells. Previous studies demonstrate that cytokine-induced memory-like NK cells that are preactivated by IL-12, IL-15, and IL-18 have enhanced effector functions and long life span in vivo. Here, we investigated the effects of IL-12/18-preactivated and IL-12/15/18-preactivated donor NK cells on GVL and aGVHD in a murine model of allo-HSCT. We found that both IL-12/18- and IL-12/15/18-preactivated NK cells mediated stronger GVL effect than control NK cells mainly due to their elevated activation/cytotoxicity and sustained proliferative potential. Interestingly, we observed that although both IL-12/18- and IL-12/15/18-preactivated NK cells significantly inhibited severe aGVHD, only the IL-12/18-preactivated NK cells maintained the beneficial effect of donor NK cells on mild aGVHD. The IL-12/15/18-preactivated NK cell infusion accelerated aGVHD in the fully-mismatched mild aGVHD model. Our results demonstrated that IL-12/18-preactivated NK cells displayed sustained and enhanced GVL functions, and could mitigate aGVHD despite the severity of the disease. IL-12/18-preactivated donor NK cell infusion may be an effective and safe adoptive therapy after allo-HSCT.

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Immunosuppressive therapy alleviates murine cytomegalovirus recurrence by reducing TNF-α post cell transplantation with lethal GVHD

Cited by 4 publications

References 46 publications

Cytomegalovirus Pneumonia in Inflammatory Bowel Disease: Literature Review and Clinical Recommendations

Cytomegalovirus Pneumonia in Inflammatory Bowel Disease: Literature Review and Clinical Recommendations

Manipulation of Viral MicroRNAs as a Potential Antiviral Strategy for the Treatment of Cytomegalovirus Infection

IL‐12/IL‐18‐preactivated donor NK cells enhance GVL effects and mitigate GvHD after allogeneic hematopoietic stem cell transplantation

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