KSHV infects B lymphocytes and establishes a predominantly latent infection. The detailed process and the mechanism underlying the establishment of latent infection remain elusive. After a KSHV particle enters a host cell, the virus undergoes D N A replication which results in accumulation of the viral genome to 50-100 copies per cell prior to establishment of latency. Little is known regarding the mode of the abortive viral replication and the regulation mechanism. ORF K8 encodes a nuclear protein of the bZip family. Gur study using K8-null recombinant virus demonstrated a role of KS in initial viral DNA replication following de novo KSHV Infection. K8-null viruses exhibit much lower viral genome copy numbers in comparison to wild type viruses when infecting 293T, HFF and HMVEC cells. The role of K8 in the early stage of de novo infection provides insights into the so-called

Public Health Relevance

Viral replication following de novo infection leads to an increase in viral genome number and is important for establishment of KSHV latency. This proposal will investigate this less explored event during the early stages of KSHV infection. The results of the study would provide an insight into the mechanism of this mode of replication which will leads to new strategies and therapies against KSHV-mediated diseases.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
1P01CA174439-01A1
Application #
8541136
Study Section
Special Emphasis Panel (ZCA1-RPRB-2 (J1))
Project Start
2013-05-08
Project End
2018-04-30
Budget Start
2013-05-08
Budget End
2014-04-30
Support Year
1
Fiscal Year
2013
Total Cost
$349,226
Indirect Cost
$76,123
Name
University of Pennsylvania
Department
Type
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Shukla, Sanket Kumar; Jha, Hem Chandra; El-Naccache, Darine W et al. (2016) An EBV recombinant deleted for residues 130-159 in EBNA3C can deregulate p53/Mdm2 and Cyclin D1/CDK6 which results in apoptosis and reduced cell proliferation. Oncotarget 7:18116-34
Jha, Hem Chandra; Banerjee, Shuvomoy; Robertson, Erle S (2016) The Role of Gammaherpesviruses in Cancer Pathogenesis. Pathogens 5:
Sun, Zhiguo; Jha, Hem Chandra; Pei, Yong-Gang et al. (2016) Major Histocompatibility Complex Class II HLA-DRα Is Downregulated by Kaposi's Sarcoma-Associated Herpesvirus-Encoded Lytic Transactivator RTA and MARCH8. J Virol 90:8047-58
Lieberman, Paul M (2016) Epigenetics and Genetics of Viral Latency. Cell Host Microbe 19:619-28
Jha, Hem C; Pei, Yonggang; Robertson, Erle S (2016) Epstein-Barr Virus: Diseases Linked to Infection and Transformation. Front Microbiol 7:1602
Huang, Hongda; Deng, Zhong; Vladimirova, Olga et al. (2016) Structural basis underlying viral hijacking of a histone chaperone complex. Nat Commun 7:12707
Gandhi, Jaya; Gaur, Nivedita; Khera, Lohit et al. (2015) COX-2 induces lytic reactivation of EBV through PGE2 by modulating the EP receptor signaling pathway. Virology 484:1-14
Uppal, Timsy; Jha, Hem C; Verma, Subhash C et al. (2015) Chromatinization of the KSHV Genome During the KSHV Life Cycle. Cancers (Basel) 7:112-42
Jha, Hem C; Yang, Karren; El-Naccache, Darine W et al. (2015) EBNA3C regulates p53 through induction of Aurora kinase B. Oncotarget 6:5788-803
Tsai, Kevin; Messick, Troy E; Lieberman, Paul M (2015) Disruption of host antiviral resistances by gammaherpesvirus tegument proteins with homology to the FGARAT purine biosynthesis enzyme. Curr Opin Virol 14:30-40

Showing the most recent 10 out of 30 publications