Human Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV) are the leading etiological agents that cause morbidity and mortality in immune compromised patients. Currently, we do not have good animal models to study these oncogenic human pathogens. Closely related to human KSHV and EBV, murine gamma herpesvirus 68 infects laboratory mice, undergoes robust lytic replication in the lung and establishes persistent infection in the spleen. This provides an excellent small animal model to study gamma herpesvirus infection in vivo. However, murine gamma herpesvirus 68 infection causes limited pathogenesis in laboratory mouse strains, offering minimal insights into diseases, e.g., cancers associated with KSHV and EBV. The goal of this study is to develop a surrogate system that enables the interrogation of host-virus interactions in virally-induced tumorigenesis, in the context of viral infection. Accordingly, the specific aims of this proposal are to: 1) enginer recombinant murine gamma herpesvirus 68 that carries the prominent KSHV oncogene, kGPCR, and examine viral replication in culture and infection in mice, and 2) to evaluate the tumorigenicity of recombinant gamma herpesvirus 68 in normal and immune- compromised mice, focusing on lymphoproliferative and Kaposi's sarcoma-like diseases. This study will provide a valuable platform to dissect viral oncogenesis that is truly induced during viral infection.
Human Kaposi's sarcoma-associated herpesvirus is the leading etiological agent that causes morbidity and mortality in immune compromised patients and currently, we do not have good animal models to study this oncogenic human pathogen. The goal of this study is to develop a surrogate system that enables the interrogation of host-virus interactions in virally-induced tumorigenesis, in the context of viral infection. This study will provide a valuable platform to dissect viral oncogenesi that is truly induced during viral infection.
| Zhao, Jun; He, Shanping; Minassian, Arlet et al. (2015) Recent advances on viral manipulation of NF-?B signaling pathway. Curr Opin Virol 15:103-11 |
| He, Shanping; Zhao, Jun; Song, Shanshan et al. (2015) Viral pseudo-enzymes activate RIG-I via deamidation to evade cytokine production. Mol Cell 58:134-46 |
| Minassian, Arlet; Zhang, Junjie; He, Shanping et al. (2015) An Internally Translated MAVS Variant Exposes Its Amino-terminal TRAF-Binding Motifs to Deregulate Interferon Induction. PLoS Pathog 11:e1005060 |
| Zhang, Junjie; Zhu, Lining; Lu, Xiaolu et al. (2015) Recombinant Murine Gamma Herpesvirus 68 Carrying KSHV G Protein-Coupled Receptor Induces Angiogenic Lesions in Mice. PLoS Pathog 11:e1005001 |
