A Dynamic Model for Induced Reactivation of Latent Virus

Grace M. Kepler
Center for Research in Scientific Computation
North Carolina State University

There is increasing evidence in the literature for the importance of 
polymicrobial infections in which microorganisms interact in a synergistic 
fashion, impacting both pathogenesis and maintenance of health. Recent 
experiments have shown that the spent media from gram negative bacteria 
cultures, such as P. Gingivalis and P. Intermedia can induce latent herpes 
viruses to begin lytic replication. A shift in the balance of the flora 
often controlled by the intact immune system may reflect significant 
morbidity particularly in an immune suppressed host.

In this talk, I will report on a preliminary deterministic mathematical 
model to describe reactivation of latent virus by chemical inducers. In
particular, we apply this model to the reactivation of latent Kaposi's
Sarcoma-associated Herpese Virus (KSHV) in BCBL-1 cell cultures with 
butyrate as the inducing agent. Our preliminary model yields good 
qualitative agreement with cell viability data for KSHV induced by 
butyrate. These initial results suggest the need for further experiments 
designed explicitly to support model development and validation. 
Application of this model to other latent viruses, such as EBV, would 
provide information about the similarities and differences among latent 
virus systems. Use of this and future models with other inducers may 
also provide extremely valuable clinical information about induction 
mechanisms.