Research on the oral biology of AIDS and the oral complications associated with AIDS has been hampered by the lack of relevant animal models. In particular, the devastating malignancies, such as Kaposi's ? Sarcoma (KS) that develop in conjunction with HIV-induced immunosuppression have been difficult to model due to the complicated interactions that are believed to occur between multiple pathogenic agents. The objective for this exploratory project is to develop a simian model for AIDS-related oral malignancies, including AIDS-KS. This work is based on our discovery of the macaque homolog of the KS-associated ? herpesvirus (KSHV) which is believed to be an important factor in the development of retroperitoneal fibromatosis (RF), a KS-like tumor of macaques. We have identified the macaque herpesvirus, called retroperitoneal fibromatosis herpesvirus (RFHV), in saliva of macaques and propose to develop strategies to purify RFHV from saliva and establish cell infection systems. We also propose to identify the sites of replication and residence of RFHV in oral tissues. This will be done in conjunction with an ongoing evaluation of HIV prevention and therapeutic strategies in macaques at the Washington National Primate Research Center (WaNPRC). Secondly, we propose to test the ability of RFHV to infect primary macaque and human cell cultures derived from oral tissues in conjunction with the Tissue Distribution Program of the WaNPRC and the Cell Culture Core laboratory of the Comprehensive Center for Oral Health Research at the School of Dentistry, UW. Our hypothesis is that interaction of retroviruses and herpesviruses within the oral environment plays an important role in the development of AIDS-KS/SAIDS-RF. The rationale for this work is to provide the knowledge-base and virus resources necessary for the establishment of such a KS model. Although the proposed study is exploratory and high risk, it is also highly significant since it could lead to the development of a very important and relevant macaque model of KS. Such a model could directly impact the prevention, diagnosis, and treatment of this devastating human disease. ? ?
| Howard, Kellie; Cherezova, Lidia; DeMaster, Laura K et al. (2017) ORF73 LANA homologs of RRV and MneRV2 contain an extended RGG/RG-rich nuclear and nucleolar localization signal that interacts directly with importin ?1 for non-classical nuclear import. Virology 511:152-164 |
| Cherezova, Lidia; Burnside, Kellie L; Rose, Timothy M (2011) Conservation of complex nuclear localization signals utilizing classical and non-classical nuclear import pathways in LANA homologs of KSHV and RFHV. PLoS One 6:e18920 |
