| Abstract |
Dr. Campbell and his laboratory have
sought to develop a genetic complementation system for retroviral
RNase H as a model for studies of Human Immunodeficiency Virus
(HIV) type 1 RNase H. This will allow a) the use mutagenic
screens to predict HIV (viral) RNase H gene mutations which
continue to support cell growth and b) the development an
in vivo screening system to identify new anti-viral drugs
targeted against RNase H. The remarkable similarity between
M-MuLV, HIV and HBV RT, specifically their encoded RNases
H, has allowed him to extend his studies of viral RNases H
to include HBV. Sequence comparisons of retroviral and hepadnaviral
RTs have revealed significant homologies that indicate important
phylogenetic and functional relationships exists between these
viruses. A number of drugs effective at inhibiting HBV P protein
(RT) effectively inhibit the corresponding HIV RT enzyme.
This observation allows studies of one enzyme to serve as
a model for studies of the other in evaluating therapeutically
useful drugs and in defining drug resistant genetic mutants.
Dr. Campbell has succeeded in developing two viral based genetic
rescue systems. They set the stage for more critical analyses
of viral gene fragments. He foresees developing these systems
to predict important mutations that when introduced into the
viral genome may be important in pathogenesis and viral replication
and fitness. They may also provide insight into candidate
mutations which may arise in nature and confer resistance
and cross-resistance to a number of promising candidate drugs.
The systems therefore may become useful for developing further
anti-viral therapeutics. Dr. Campbell has successfully secured
NIH fellowship funding (F31 GM20760) and has other applications
pending.
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