Role of Viral Chemokine Receptors in Cytomegalovirus Latency

病毒趋化因子受体在巨细胞病毒潜伏期中的作用

• 批准号: 9284685
• 负责人: Rhonda D Cardin
• 金额: $ 13.72万
• 依托单位: LOUISIANA STATE UNIV A&M COL BATON ROUGE
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-05 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9284685
• 关键词: Role; Viral; Chemokine; Receptors; Cytomegalovirus

Project Summary/Abstract Reactivation of Human Cytomegalovirus (HCMV) from latency is the most common infectious complication in bone marrow transplant patients, with significant morbidity and mortality. Very little is known about the viral/host interactions governing the establishment and maintenance of long term HCMV infection. The long-term goal is to identify the viral and host mechanisms that lead to the development of CMV latency. The objective of this proposal is to determine the role of the CMV-encoded chemokine receptors in the establishment of latency in progenitor myeloid lineage cells and to identify the host signaling pathways that promote CMV establishment of latency. The central hypothesis is that the CMV-encoded chemokine receptors activate host signaling pathways which aid in the establishment of latency during in vivo infection. Project Summary: Our hypothesis is based on strong preliminary data which demonstrates that murine CMV (MCMV) lacking M33 does not efficiently establish latent infection and that M33-deficient viruses which express the HCMV-encoded chemokine receptors, UL33 or US28, complements this latency defect in vivo. Three specific aims will be pursued: 1) Identify the myeloid lineage cell type which requires M33 for the establishment and/or maintenance of CMV latency in vivo, 2) Identify the mechanisms underlying the role of M33 during infection in monocytes, and 3) Identify the M33-mediated signaling pathway (s) required for establishment and/or maintenance of CMV latency. This aim will utilize specific M33 mutant viruses coupled with microarray analysis to identify signaling pathways which are modulated by M33 and US28. The approach is innovative, and uses a multifaceted approach to identify the host and viral factors involved in the establishment and/or maintenance of CMV latency in myeloid lineage cells. The proposed research is significant, because it is expected to lead to the development of therapeutic strategies aimed at preventing CMV latency and complications due to reactivation of latent CMV. Relevance to Public Health: The new knowledge obtained will lead to the prevention of CMV latency and reactivation in immunocompromised patients, such transplant patients, neonates, and AIDS patients, where CMV infection leads to significant morbidity and mortality.

项目概要/摘要 人类巨细胞病毒 (HCMV) 从潜伏期重新激活是最常见的 骨髓移植患者的感染性并发症，具有显着的发病率和 死亡。对于控制病毒/宿主的相互作用知之甚少 长期HCMV感染的建立和维持。长期目标是 确定导致 CMV 潜伏期发展的病毒和宿主机制。 该提案的目的是确定 CMV 编码的趋化因子的作用 受体在祖髓系细胞中建立潜伏期并 确定促进 CMV 建立潜伏期的宿主信号通路。这 中心假设是 CMV 编码的趋化因子受体激活宿主信号传导 有助于体内感染期间建立潜伏期的途径。项目 摘要：我们的假设基于强有力的初步数据，这些数据表明 缺乏 M33 的鼠 CMV (MCMV) 不能有效地建立潜伏感染，并且 M33 缺陷型病毒，表达 HCMV 编码的趋化因子受体、UL33 或 US28，补充了体内的这种潜伏期缺陷。将追求三个具体目标：1) 鉴定需要 M33 建立的骨髓谱系细胞类型和/或 体内 CMV 潜伏期的维持，2) 确定其作用的机制 单核细胞感染过程中的 M33，以及 3) 识别 M33 介导的信号通路 (s) 建立和/或维持 CMV 潜伏期所需的。这一目标将利用 特定的 M33 突变病毒与微阵列分析相结合以识别信号传导 受 M33 和 US28 调节的途径。该方法具有创新性，并使用 多方面的方法来确定建立所涉及的宿主和病毒因素 和/或维持骨髓谱系细胞中 CMV 潜伏期。这 拟议的研究意义重大，因为它预计将导致发展 旨在预防 CMV 潜伏期和并发症的治疗策略 潜伏的 CMV 重新激活。与公共卫生的相关性：获得的新知识 将导致免疫功能低下的 CMV 潜伏期和再激活的预防 患者，如移植患者、新生儿和艾滋病患者，其中 CMV 感染 导致显着的发病率和死亡率。

项目成果

Characterization of murine cytomegalovirus infection and induction of calcification in Murine Aortic Vascular Smooth Muscle Cells (MOVAS).

• DOI: 10.1016/j.jviromet.2021.114270
• 发表时间: 2021-11
• 期刊: Journal of virological methods
• 影响因子: 3.1
• 作者: Bonavita CM;White TM;Stanfield BA;Cardin RD
• 通讯作者: Cardin RD

Tissue-specific control of latent CMV reactivation by regulatory T cells.

• DOI: 10.1371/journal.ppat.1006507
• 发表时间: 2017-08
• 期刊: PLoS pathogens
• 影响因子: 6.7
• 作者: Almanan M;Raynor J;Sholl A;Wang M;Chougnet C;Cardin RD;Hildeman DA
• 通讯作者: Hildeman DA

The Viral G-Protein-Coupled Receptor Homologs M33 and US28 Promote Cardiac Dysfunction during Murine Cytomegalovirus Infection.

• DOI: 10.3390/v15030711
• 发表时间: 2023-03-09
• 期刊: Viruses
• 作者: Bonavita CM;White TM;Francis J;Farrell HE;Davis-Poynter NJ;Cardin RD
• 通讯作者: Cardin RD

Murine Cytomegalovirus Spreads by Dendritic Cell Recirculation.

• DOI: 10.1128/mbio.01264-17
• 发表时间: 2017-10-03
• 期刊: mBio
• 影响因子: 6.4
• 作者: Farrell HE;Bruce K;Lawler C;Oliveira M;Cardin R;Davis-Poynter N;Stevenson PG
• 通讯作者: Stevenson PG