Eylem Seç
Regulation Of Human Cytomegalovirus Major Immediate Early Gene Expression During Lytic Replication
Başlık:
Regulation Of Human Cytomegalovirus Major Immediate Early Gene Expression During Lytic Replication
Yazar:
Arend, Kyle C., author.
ISBN:
9780438033504
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (140 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 79-10(E), Section: B.
Advisors: Nathaniel J. Moorman; Mark T. Heise Committee members: Stanley M. Lemon; Cary A. Moody; Matt C. Wolfgang.
Özet:
Human cytomegalovirus (HCMV) is a significant cause of disease in immune-compromised adults and immune naive newborns. No vaccine exists to prevent HCMV infection, and current antiviral therapies have toxic side effects that limit the duration and intensity of their use. Expression of the HCMV major immediate early (MIE) proteins, IE1 and IE2, is critical for the establishment of lytic infection and reactivation from viral latency. Defining the mechanisms controlling IE1 and IE2 expression is therefore important for understanding how HCMV regulates its replicative cycle. In Chapter 2 we identified several novel transcripts encoding full-length IE1 and IE2 proteins during HCMV lytic replication. While the canonical MIE mRNA was the most abundant transcript at immediate early times, the novel MIE transcripts accumulated to equivalent levels as the known MIE transcript later in infection and were found associated with polyribosomes. These results expand our understanding of the sequences controlling IE1 and IE2 expression by defining novel transcriptional units controlling the expression of full-length IE1 and IE2 proteins. Beyond transcriptional regulation, relatively little is known about the post-transcriptional mechanisms that control IE1 and IE2 protein synthesis. In Chapter 3 we found that the canonical MIE 5' untranslated region (5' UTR) has a positive role in translation control of reporter genes during transfection. We also found that the MIE 5'UTR was necessary for efficient IE1 and IE2 mRNA translation as well as viral replication during infection. These results demonstrate that the shared 5' UTR of the IE1 and IE2 mRNA is a critical determinant of efficient HCMV replication. Virus-induced changes in infected cells are often driven by changes in cellular kinase activity. In Chapter 4 we applied a kinase capture technique, MIB-MS kinome profiling, to quantitatively measure perturbations in >240 cellular kinases simultaneously in cells infected with HCMV. Based on the kinome data, we identified three compounds currently being studied in clinical trials that inhibited HCMV replication. These results show the utility of MIB-MS kinome profiling for identifying existing kinase inhibitors that can potentially be repurposed as novel antiviral drugs to limit the time and cost of new antiviral drug development.
Notlar:
School code: 0153
Tüzel Kişi Ek Girişi:
Mevcut:*
Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(678361.1) | 678361-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
On Order
Liste seç
Bunu varsayılan liste yap.
Öğeler başarıyla eklendi
Öğeler eklenirken hata oldu. Lütfen tekrar deneyiniz.
:
Select An Item
Data usage warning: You will receive one text message for each title you selected.
Standard text messaging rates apply.