考拉逆转录病毒(KoRV)感染后考拉基因表达变化的初步研究以及 KoRV 发病机制的潜在生物标记物的鉴定。

IF 2.3 2区 农林科学 Q1 VETERINARY SCIENCES
Lipi Akter, Md Abul Hashem, Mohammad Enamul Hoque Kayesh, Md Arju Hossain, Fumie Maetani, Rupaly Akhter, Kazi Anowar Hossain, Md Haroon Or Rashid, Hiroko Sakurai, Takayuki Asai, M Nazmul Hoque, Kyoko Tsukiyama-Kohara
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引用次数: 0

摘要

背景:考拉逆转录病毒(KoRV)是考拉的主要病原体:考拉逆转录病毒(KoRV)是考拉的一种主要病原体,以内源性(KoRV-A)和外源性(KoRV-A 至 I 和 K 至 M)两种形式存在,可导致多种疾病表型,包括癌变和免疫抑制。然而,不同的 KoRV 亚型与癌变之间的直接关联仍然未知。我们采用高通量 RNA-seq 方法对携带内源性(KoRV-A)和外源性(KoRV-A、B 和 C)亚型的考拉外周血单核细胞(PBMC)进行了差异表达基因(DEG)分析。研究人员从三只健康考拉身上获取了血清白细胞介素,其中一只感染了内源性亚型(KoRV-A;第一组),两只感染了外源性亚型(KoRV-B 和/或 KoRV-C;第二组)。此外,还收集并检查了六只感染 KoRV 的死亡考拉(K1- K6)的脾脏样本(n = 6)和一只活考拉(K7)的血液样本(n = 1),以验证研究结果:结果:所有考拉的内源性 KoRV-A 亚型均呈阳性,8 只考拉的 KoRV-B 和/或 KoRV-C 均呈阳性。所有考拉都检测到了 KoRV gag、pol 和 env 基因的转录。与只感染了 KoRV-A 的考拉相比,在感染了 KoRV-B 或 KoRV-B 和 -C 亚型的考拉中观察到细胞因子和免疫抑制基因的上调。我们发现有550个DEG特征存在显著的失调(绝对p 2折叠变化(FC)> 1.5),其中77.6%和22.4%的DEG上调(log2FC > 1.5)和下调(log2FC 2 FC 结论):因此,可以得出结论:多种 KoRV 亚型会影响考拉的疾病进展,而预测的枢纽基因可能是有希望的发病机制预后生物标志物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
A preliminary study of gene expression changes in Koalas Infected with Koala Retrovirus (KoRV) and identification of potential biomarkers for KoRV pathogenesis.

Background: Koala retrovirus (KoRV), a major pathogen of koalas, exists in both endogenous (KoRV-A) and exogenous forms (KoRV-A to I and K to M) and causes multiple disease phenotypes, including carcinomas and immunosuppression. However, the direct association between the different KoRV subtypes and carcinogenesis remains unknown. Differentially expressed gene (DEG) analysis of peripheral blood mononuclear cells (PBMCs) of koalas carrying both endogenous (KoRV-A) and exogenous (KoRV-A, B, and C) subtypes was performed using a high-throughput RNA-seq approach. PBMCs were obtained from three healthy koalas: one infected with endogenous (KoRV-A; Group I) and two infected with exogenous (KoRV-B and/or KoRV-C; Group II) subtypes. Additionally, spleen samples (n = 6) from six KoRV-infected deceased koalas (K1- K6) and blood samples (n = 1) from a live koala (K7) were collected and examined to validate the findings.

Results: All koalas were positive for the endogenous KoRV-A subtype, and eight koalas were positive for KoRV-B and/or KoRV-C. Transcription of KoRV gag, pol, and env genes was detected in all koalas. Upregulation of cytokine and immunosuppressive genes was observed in koalas infected with KoRV-B or KoRV-B and -C subtypes, compared to koalas infected with only KoRV-A. We found 550 DEG signatures with significant (absolute p < 0.05, and absolute log2 Fold Change (FC) > 1.5) dysregulation, out of which 77.6% and 22.4% DEGs were upregulated (log2FC > 1.5) and downregulated (log2FC <  - 1.5), and downregulated (logFC <  - 1), respectively. We identified 17 unique hub genes (82.3% upregulated and 17.7% down-regulated), with KIF23, CCNB2, POLR3F, and RSL24D1 detected as the potential hub genes modified with KoRV infection. Real-time RT-qPCR was performed on seven koalas to ascertain the expression levels of four potential hub genes, which were subsequently normalized to actin copies. Notably, all seven koalas exhibited distinct expression signatures for the hub genes, especially, KIF23 and CCNB2 show the highest expression in healthy koala PBMC, and POLR3F shows the highest expression in koala with lymphoma (K1).

Conclusion: Thus, it can be concluded that multiple KoRV subtypes affect disease progression in koalas and that the predicted hub genes could be promising prognostic biomarkers for pathogenesis.

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来源期刊
BMC Veterinary Research
BMC Veterinary Research VETERINARY SCIENCES-
CiteScore
4.80
自引率
3.80%
发文量
420
审稿时长
3-6 weeks
期刊介绍: BMC Veterinary Research is an open access, peer-reviewed journal that considers articles on all aspects of veterinary science and medicine, including the epidemiology, diagnosis, prevention and treatment of medical conditions of domestic, companion, farm and wild animals, as well as the biomedical processes that underlie their health.
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