Genes Determining the Course of Virus Persistence in the Liver: Lessons from Murine Infection with Lymphocytic Choriomeningitis Virus

Lang, Philipp A.; Recher, Mike; Häussinger, Dieter; Lang, Karl S.

doi:10.1159/000320549

Cited by 14 publications

(13 citation statements)

References 116 publications

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“…In addition, SAMSN1 expression is upregulated by signaling factors that promote the activation and differentiation of B-cells (11,13). The present study hypothesized that chronic inflammation is caused by H. pylori infection-induced dysregulation of immune function and aberrant expression of SAMSN1 (38,39). However, this hypothesis is not fully supported by the present findings, as detailed information regarding H. pylori infection was not collected.…”

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confidence: 68%

Prognostic relevance of SAMSN1 expression in gastric cancer

et al. 2016

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Abstract.The prognosis for patients with advanced gastric cancer (GC) remains poor. The identification of biomarkers relevant to the recurrence and metastasis of GC is advantageous for stratifying patients and proposing novel molecular targets. In the present study the oncological roles of SAM domain, SH3 domain and nuclear localization signals 1 (SAMSN1), a mediator of B-cell function, were elucidated in GC. The expression and methylation status of SAMSN1 were investigated in a panel of 11 GC cell lines. Immunohistochemical staining was performed to determine the pattern of SAMSN1 protein expression in gastric tissues. The prognostic impact of SAMSN1 expression was determined by analyzing 175 pairs of surgically resected gastric tissues. A marked decrease in the level of SAMSN1 mRNA was detected in 8/11 GC cell lines as compared with that in a non-transformed intestinal epithelium cell line (FHs 74) without promoter methylation. The mean expression level of SAMSN1 mRNA was reduced in GC tissues compared with normal adjacent tissues, an observation that was independent of tumor differentiation. The pattern of SAMSN1 protein expression was significantly correlated with that of SAMSN1 mRNA. Low SAMSN1 mRNA expression was significantly associated with tumor size (>60 mm; P=0.026) and shorter overall survival times (P=0.004). Multivariate analysis identified low SAMSN1 mRNA expression as an independent prognostic factor for poor overall survival (hazard ratio, 1.80; 95% confidence interval, 1.07-3.05; P= 0.025). The difference in survival between the low and high SAMSN1 expression groups was more marked in patients with stage II/III GC compared to those with stage IV GC. In patients with stage II/III GC who underwent curative surgery, low SAMSN1 expression was associated with reduced disease free survival times. The results of the present study indicate that downregulation of SAMSN1 transcription may affect the progression and recurrence of GC, and therefore may represent a novel biomarker of GC.

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confidence: 68%

Prognostic relevance of SAMSN1 expression in gastric cancer

et al. 2016

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“…Host genetics seem to play a role in disease development, 31,43 which is not unique to PCV2-associated diseases, as this has also been observed for other viral diseases. 44 …”

Section: Resultsmentioning

confidence: 99%

T-cell reprogramming through targeted CD4-coreceptor and T-cell receptor expression on maturing thymocytes by latentCircoviridaefamily member porcine circovirus type 2 cell infections in the thymus

Klausmann

Sydler

Summerfield³

et al. 2015

Emerging Microbes & Infections

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Although porcine circovirus type 2 (PCV2)-associated diseases have been evaluated for known immune evasion strategies, the pathogenicity of these viruses remained concealed for decades. Surprisingly, the same viruses that cause panzootics in livestock are widespread in young, unaffected animals. Recently, evidence has emerged that circovirus-like viruses are also linked to complex diseases in humans, including children. We detected PCV2 genome-carrying cells in fetal pig thymi. To elucidate virus pathogenicity, we developed a new pig infection model by in vivo transfection of recombinant PCV2 and the immunosuppressant cofactor cyclosporine A. Using flow cytometry, immunofluorescence and fluorescence in situ hybridization, we found evidence that PCV2 dictates positive and negative selection of maturing T cells in the thymus. We show for the first time that PCV2-infected cells reside at the corticomedullary junction of the thymus. In diseased animals, we found polyclonal deletion of single positive cells (SPs) that may result from a loss of major histocompatibility complex class-II expression at the corticomedullary junction. The percentage of PCV2 antigen-presenting cells correlated with the degree of viremia and, in turn, the severity of the defect in thymocyte maturation. Moreover, the reversed T-cell receptor/CD4-coreceptor expression dichotomy on thymocytes at the CD4+CD8interm and CD4SP cell stage is viremia-dependent, resulting in a specific hypo-responsiveness of T-helper cells. We compare our results with the only other better-studied member of Circoviridae, chicken anemia virus. Our data show that PCV2 infection leads to thymocyte selection dysregulation, adding a valuable dimension to our understanding of virus pathogenicity.

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“…The non-cytopathic arenaviruses propagate rapidly without directly harming susceptible tissues. Rather, it is the immune response against infected cells that may cause severe tissue damage and disease symptoms89. Arenaviruses can infect humans and disease outcome depends on the specific strain.…”

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confidence: 99%

Spatiotemporally restricted arenavirus replication induces immune surveillance and type I interferon-dependent tumour regression

Kalkavan

Sharma

Kasper³

et al. 2017

Nat Commun

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Immune-mediated effector molecules can limit cancer growth, but lack of sustained immune activation in the tumour microenvironment restricts antitumour immunity. New therapeutic approaches that induce a strong and prolonged immune activation would represent a major immunotherapeutic advance. Here we show that the arenaviruses lymphocytic choriomeningitis virus (LCMV) and the clinically used Junin virus vaccine (Candid#1) preferentially replicate in tumour cells in a variety of murine and human cancer models. Viral replication leads to prolonged local immune activation, rapid regression of localized and metastatic cancers, and long-term disease control. Mechanistically, LCMV induces antitumour immunity, which depends on the recruitment of interferon-producing Ly6C+ monocytes and additionally enhances tumour-specific CD8+ T cells. In comparison with other clinically evaluated oncolytic viruses and to PD-1 blockade, LCMV treatment shows promising antitumoural benefits. In conclusion, therapeutically administered arenavirus replicates in cancer cells and induces tumour regression by enhancing local immune responses.

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Genes Determining the Course of Virus Persistence in the Liver: Lessons from Murine Infection with Lymphocytic Choriomeningitis Virus

Cited by 14 publications

References 116 publications

Prognostic relevance of SAMSN1 expression in gastric cancer

Prognostic relevance of SAMSN1 expression in gastric cancer

T-cell reprogramming through targeted CD4-coreceptor and T-cell receptor expression on maturing thymocytes by latentCircoviridaefamily member porcine circovirus type 2 cell infections in the thymus

Spatiotemporally restricted arenavirus replication induces immune surveillance and type I interferon-dependent tumour regression

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