ANNUAL REPORT - Department of Biotechnology

cause for concern. The modeling studies have led to
elucidation of differences between PfALAD and host
enzyme at the active site and metal binding site.
These results would be useful in designing molecules
to specifically inhibit PfALAD. Further it was found
that rifampicin inhibited the malaria parasite
apicoplast RNA polymerase. Studies in mice infected
with P. berghei, revealed that rifampicin at the
optimum dose could give around 50% protection, the
end point being parasite load and mortality. Further
studies have been carried out to establish the
production.
Infectious Disease Biology
Two meetings of the Task Force were organized
th
during the year. Priority areas for 11 Plan period
were identified. A total of 52 new project proposals
were considered and 24 were recommended for
support. Besides, advertisements for call on
proposals were made in the areas of HIV/AIDS &
microbicides, Chikungunya research and Virus
Research Programmes. Some of the significant
progress are highlighted below:
HIV/AIDS
Studies on the molecular basis of CTL dysfunction in
HIV infection at NCCS, Pune showed that CD40 and
IL-12 in priming of CD4+ cells provide help in CD8+
cells in CTL maturation. Appropriate CD4+ T cell help
is necessary for maturation of even fully expanded
CD8+ T cells into functional CTLs. The importance of
IFN-γ in inducing expression of CTL effector
molecules, perforin and granzyme has been already
demonstrated. Finding means of rescuing an
impaired CTL functions may devise an
immunotherapeutic strategy towards control HIV
replication or to boost existing strategies. At the same
institute studies on extracellular Tat Mediated
inhibition of HIV-1 replication has led towards
identification of a novel interaction of SMAR1 with the
host protein TAP (HIV-1 Tat activating protein).
SMAR1 peptide may be used to block the
transcription complex formation between Tat-TAP
and SMAR1.
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Towards identification and characterization of CD4
Independent HIV receptors on spermatozoa at
NIRRH, Mumbai, human mannose receptor has
been identified as CD4 independent HIV receptor
present on spermatozoa. Its differential expression
on the spermatozoa may determine the possible risk
of sexual transmission of HIV. Results also indicate
the need for revised strategy for prevention of sexual
transmission of HIV.
Towards identification and characterization of anti-
HIV compounds in Indian marine bivalves at NCCS,
Pune, NIO, Goa & ICGEB, New Delhi, new anti-HIV
compounds have been isolated, identified and
characterized. Application for filing patent is under
progress.
Studies on HIV-1 pathogenesis and the role of
integrase in reverse transcription and nuclear
transport of viral genome at CDFD, Hyderabad
suggested that Integrase play a critical role in reverse
transcription in addition to its role in integration.
Understanding of its role in early viral life cycle may
help to develop new effective antiviral molecules.
Work on functional analysis of the NF-KB
polymorphism in the terminal repeat of HIV-1
subtype-C viruses at JNCASR, Bangalore revealed
that the NF-kB polymorphism unique for subtype C
promoter (C-LTR) contributes significantly for gene
expression regulation. A novel strategy has been
developed to prepare Tat protein with higher
efficiency more importantly by preserving the
biological functions of the recombinant protein intact.
Studies on development of a lentivirus (HIV-2, Indian
Isolate) based high efficiency gene transfer vector
were carried out at ACTREC, Mumbai. An indigenous
gene transfer vector is in final stages of development
with novel features of versatile multiple cloing site
with expanded cloning capability.
Core Immunology Lab
Efforts were continued towards establishing an
immunology core/clinical laboratory to evaluate HIV
vaccine elicited immune responses at ICGEB, New
Research and Development