Viral RNPs, mRNA Stability and Export

非编码核rna在携带三种转化疱疹病毒的淋巴样细胞中的作用正在被研究。eb病毒（EBV）感染并转化人类B细胞，是传染性单核细胞增多症的病原体，也与几种人类癌症有关。猴疱疹病毒在新世界猴体内诱发致命的淋巴瘤和白血病，并在培养物中转化人和猴的T淋巴细胞，导致成熟的活化表型。卡波西肉瘤相关疱疹病毒（KSHV）折磨艾滋病和其他免疫功能低下的患者，像其他疱疹病毒一样，在裂解期激活之前以潜伏形式存在。在转化细胞中表达的病毒基因产物有2种ebv编码的EBERs和7种猴血蜱编码的hrs；然而，他们是

The roles of non-coding nuclear RNAs in lymphoid cells harboring three transforming herpesviruses are being investigated. Epstein-Barr virus (EBV) infects and transforms human B cells and is the causative agent of infectious mononucleosis, as well as being associated with several human cancers. Herpesvirus saimiri induces fatal lymphomas and leukemias in New World monkeys and transforms human and monkey T lymphocytes in culture, resulting in a mature, activated phenotype. Kaposi sarcoma-associated herpesvirus (KSHV) afflicts AIDS and other immunocompromised patients and, like other herpesviruses, persists in a latent form until activation of the lytic phase. Among the few viral gene products expressed in transformed cells are the two EBV-encoded EBERs and the seven H. saimiri-encoded HSURS; yet, they are not essential for viral growth or transformation. Upon induction, KSHV produces PAN, a capped, polyadenylated RNA that does not leave the nucleus. These viral RNAs are all relatively small (<1.1 kb), abundant, conserved, and associate with host proteins that - in the case of EBERs and HSURs - are autoantigens. They are therefore excellent probes for dissecting host cell pathways, as well as mechanisms of viral transformation or lytic growth. Proposed experiments will test both the hypothesis that EBERs, HSURs and PAN may perturb cellular metabolism by sequestering important host proteins, and the possibility that their RNPs perform some function critical for the virus. The molecular details of the interactions of protein L22, PKR and La with EBER1 will be probed by structural studies and nucleotide analog interference mapping. Components of the EBER2 RNP will be identified. EBERs will be examined for possible shuttling between the nucleus and cytoplasm, and their contribution to host gene expression assessed by microarray analyses, Microarray evidence that HSURs 1 and 2 enhance the activated state of transformed T cells will be confirmed in rescue experiments using lentiviral vectors, their interaction with TTP and its effects examined, and the level at which HSURs modulate host gene expression determined. RNA elements and trans-acting factors essential for PAN accumulation in the nucleus will be characterized. PAN function in KSHV lytic infection will be investigated by siRNA knockdown and/or genomic PAN deletion, followed by complementation experiments.