This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We have also recently isolated a new herpesvirus, CalHV-3 (Callithrix herpesvirus 3), from spontaneous B cell lymphomas arising in common marmosets (Callithrix jacchus), a New World primate. Like EBV, this virus can immortalize B cells in tissue culture. Sequence analysis of a 35 kb cosmid clone indicates that the virus is most appropriately categorized as a LCV, but is more distant from EBV than other LCV found in Old World primates. A viral oncogene with structural and functional similarities, but little sequence homology, to the EBV LMP1 is positionally conserved as in other gamma herpesviruses. Persistent CalHV-3 infection is present in healthy animals from two independent domestic colonies indicating that it is a naturally occurring infectious disease. A similar LCV can be identified in squirrel monkeys (Saimiri sciureus) providing further evidence that the classic paradigm for LCV evolution only in Old World primates needs to be redefined.
The specific aims of these studies are as follows:
Specific aim #1. To clone and sequence the complete CalHV-3 genome.
Specific aim #2. To identify latent infection, transformation associated viral genes expressed in CalHV-3 infected, immortalized B cells.
Specific aim #3. To identify the spectrum of New World primates naturally infected with LCV and to identify possible disease associations.
Specific Aim #4. To experimentally infect animals with CalHV-3. These studies will redefine our understanding for the evolution of oncogenic gamma herpesviruses. This model is particularly interesting since virus associated malignant disease occurs spontaneously in the natural host without overt immunosuppression. These viruses provide an important model of how LCV can cause persistent infection and contribute to malignant disease.
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