Introduction
HIV-1 is a retrovirus with RNA as the genetic material. Through a
process of reverse transcription, proviral DNA is synthesized from
viral genomic RNA. The nucleocapsid (NC) protein of HIV-1 mediates
several steps of reverse transcription by playing a role of nucleic
acid chaperone protein. HIV-1 NC protein has two conserved CCHC type
zinc finger motifs. NC protein destabilizes nucleic acids structures to
enhance the annealing of more thermodynamically favorable structures.
This chaperone function of NC protein helps in annealing of
complementary regions of two nucleic acid strands during strand
transfer steps of reverse transcription.
The direct repeat regions R present at the ends of
the viral RNA genome contain a highly structured TAR region having a
stem loop structure. The structured TAR regions have to be destabilized
by NC in order to facilitate strand annealing steps of reverse
transcription. My goal is to study NC protein – TAR RNA
interactions by using biochemical and biophysical tools including
annealing assays, circular dichroism and NMR.
Significance
HIV-1 is a causative agent of AIDS. Known drugs for AIDS target the
viral enzymes reverse transcriptase and protease, but both proteins can
mutate rapidly, without loss of enzymatic activity, to render these
drugs ineffective. The conserved CCHC type zinc finger motifs present
in NC protein are important for several steps in viral replication
cycle and are a promising target for antiviral drugs. Understanding the
interactions of NC with TAR RNA may contribute in this direction.
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