The inventors present a novel strategy for achieving pathogen opportunistic pathogenesis, with broad implications for treating infectious diseases. In a comprehensive analysis of Kaposi sarcoma-associated herpesvirus (KSHV), a medically important virus, the inventors discovered novel antiviral targets and gene function and identified opportunistic factors with dual functions of regulating both the immune environment/responses and viral reactivation/replication. This discovery includes:
A collection of KSHV mutants with inactivation or deletion of each of the 91 predicted open reading frames (91 mutant strains).
Methods and reagents (e.g. primers) for construction of the collection of KSHV mutants.
The identity of 44 KSHV essential genes, which represent potential antiviral targets (including 27 newly identified essential genes).
Methods for construction of gene-inactivation and rescued mutants, and for tagging and introducing foreign genes into the KSHV genome. These approaches can be used for vector and vaccine development.
Growth properties of viral mutants with inactivation of non-essential genes.
Methods for screening mutants in different human cell lines.
Opportunistic factors of KSHV and all other animal viruses that have dual functions as both the modulators of immune environment/response and regulators of viral reactivation/replication.
By measuring virus production in the absence of lytic induction, it is possible to identify viral open reading frames (ORFs) regulating latency and spontaneous reactivation. Identification of these “no growth attenuation” genes presents an advantage over other attenuated dispensable genes; due to the conservation of near to wild-type like growth characteristics in tissue culture, high-titers of the gene therapy vector can be attained.
This discovery shows how viral reactivation is correlated with the status of immune status/responses. Under immunocompetent conditions, the mechanism could lead to viral latency with no onset of diseases, while under immunodeficient conditions it would lead to viral active replication with full-blown viral diseases.
- Name: Laleh Shayesteh
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- Phone : 510-642-4537
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