Role of MHV68 v-cyclin in virus egress

MHV68 v-cyclin 在病毒流出中的作用

基本信息

批准号：
8807186
负责人：
SAMUEL H SPECK
金额：
$ 23.4万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-12-01 至 2016-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8807186
关键词：
1 year old 10 year old Actins Acute Adenoviruses Animal Model Apoptosis Attention B-Lymphocytes Binding Biochemical Biological Models CDK2 gene Cell Cycle Cell Cycle Progression Cell Death Induction Cell Line Cells Complex Cyclin A Cyclins Cytoskeletal Modeling Cytoskeleton DNA Viruses Defect Development Disease Environment Epithelial Cells Exhibits Foundations Future Genes Growth HIV Health Herpesviridae Herpesviridae Infections Homologous Gene Human Herpesvirus 4 Human Herpesvirus 8 In Vitro Individual Infection Life Cycle Stages Lung Lymphocyte Function Lymphoma Modeling Mus Necrosis Oncogenes Papillomavirus Phenotype Play Polyomavirus Property Proteins Rhadinovirus Role Saimiriine Herpesvirus 2 Structural Models Structure Technetium Tc 99m ciprofloxacin Transgenes Transgenic Mice Viral Virion Virus Virus Diseases Virus Replication Work base cell type gamma-2 herpesvirus gammaherpesvirus immunosuppressed in vivo insight macrophage mutant novel reactivation from latency tissue culture trafficking tumor viral cyclin

项目摘要

DESCRIPTION (provided by applicant): Gammaherpesviruses are associated with the development of lympho-proliferative disorders and lymphoma, particularly in immunosuppressed individuals. Indeed, half of the lymphomas that arise in HIV infected individuals are associated with either EBV or KSHV infection. Perturbation of host cell cycle is a common strategy employed by DNA viruses to achieve a cellular environment conducive to viral growth. Adenovirus, polyoma virus, papilloma virus, and many herpesviruses encode genes that directly alter the host cell cycle, or interact with host gene products to the same end. Rhadinoviruses (γ2-herpesviruses), such as Kaposi sarcoma-associated herpesvirus (KSHV), herpesvirus saimiri (HVS), and murine gammaherpesvirus-68 (MHV68), encode a homolog of mammalian D-type cyclins. We have previously shown that the MHV68 v-cyclin is required for: (i) efficient acute replication in the lungs of mice; and (ii) reactivation from latently infected macrophages and B cells. We have recently identified a tissue culture model that recapitulates the replication defect observed with v-cyclin null and v-cyclin CDK binding mutants in vivo. Further characterization of MHV68 replication in this tissue culture model has identified a profound defect in the egress of v-cyclin null and v-cyclin CDK binding mutants from infected cells. In this new R21 application, we propose to investigate the role that the MHV68 v-cyclin plays in virus egress/release from lung epithelial cells. The specific aims are as follows: Aim 1. Characterization of the v-cyclin null mutant MHV68 egress phenotype: 1.a Localization of virions in wt and v-cyclin mutant infected cells; 1.b Cellular localization of v-cyclin during virus infecton; 1.c Assess egress phenotype of a KSHV v-cyclin null mutant in HUVECs. Aim 2. Analysis of v-cyclin functions in the absence of MHV68 infection: 2.a Generate and characterize inducible v-cyclin expressing cell lines; 2.b Identify v-cyclin interacting partners.

描述（由适用提供）：伽马病毒病毒与淋巴增殖疾病和淋巴瘤的发展有关，尤其是在免疫抑制的个体中。实际上，在HIV感染个体中出现的一半淋巴瘤与EBV或KSHV感染有关。宿主细胞周期的扰动是DNA病毒采用的一种常见策略，以实现病毒生长的细胞环境导电。腺病毒，多瘤病毒，乳头状瘤病毒和许多疱疹病毒编码直接改变宿主细胞周期或与宿主基因产物相互作用的基因。 rhadinoviruses（γ2-疱疹病毒），例如Kaposi肉瘤相关的疱疹病毒（KSHV），疱疹病毒Saimiri（HVS）和Murine Gammaherpesvirus-68（MHV68），Encode cymamalian d-cyclins。我们先前已经表明，MHV68 V-Cyclin是需要：（i）小鼠肺中有效的急性复制；（ii）从潜在感染的巨噬细胞和B细胞重新激活。我们最近确定了一种组织培养模型，该模型概括了体内用V-胞酸蛋白空和V-胞酸蛋白CDK结合突变体观察到的复制缺陷。在该组织培养模型中，MHV68复制的进一步表征已经确定了V-Cyclin null和V-Cyclin cdk结合突变体的出口中存在深刻的缺陷。在这个新的R21应用，我们建议研究MHV68 V-Cyclin在病毒出口/从肺上皮细胞中释放中发挥作用的作用。具体目的如下：目标1。v-cyclin null突变体MHV68出口表型的表征：1。病毒在WT和V-Cyclin突变体感染细胞中的定位； 1.B病毒感染期间V-周克蛋白的细胞定位； 1.C评估HUVEC中KSHV V-Cyclin null突变体的出口表型。目标2。在没有MHV68感染的情况下，V-Cyclin功能的分析：2.a产生并表征诱导型V-Cyclin表达细胞系； 2.B识别V-Cyclin相互作用伙伴。