Research Interests:
The primary interest of our lab is HIV pathogenesis
and approaches for the prevention and treatment of AIDS. Currently,
there are three major areas of efforts: design and evaluation of
vaccines against HIV and related primate lentiviruses; structural,
functional and immunogenic properties of HIV-1 envelope proteins,
and the development and use of HIV-2/macaque models to study strategies
of therapeutic intervention.
Using SIV as a model, we have shown that immunization
with live recombinant poxvirus in combination with subunit vaccines
was able to protect macaques against infection by a pathogenic primate
lentivirus. This provides us with a basis to study the correlates
and mechanisms of protection, to define the limits of the protective
responses and to design new approaches to augment such responses.
We are also investigating to what extend such approaches could be
applied towards the development of a safe and effective vaccine
against HIV infection and AIDS in human.
One of the key targets for the development of
AIDS vaccines is the highly glycosylated surface antigen of HIV.
Evidence suggests that these carbohydrates may contribute to the
ability of the virus to escape host immune responses. We are testing
this idea by introducing site-specific mutations in selective N-linked
glycosylation sites in the env gene of HIV-1 and studying their
effects on the functional and antigenic properties of the mutant
viruses and their envelope proteins. We are also examining whether
such mutant proteins will provide better candidates for AIDS vaccines
than the fully glycosylated forms.
Finally, we have developed a highly pathogenic
isolate of HIV-2, which upon inoculation in pig-tailed macaques
induces rapid CD4 depletion and AIDS-like diseases. We are currently
studying events in the acute phase of infection leading to CD4 depletion
and attempting to define genetic determinants that contribute to
the highly pathogenic phenotype of this virus. We have also used
this model to show that post-exposure treatment with antiviral drugs,
even of limited duration, is highly effective in reducing viral
load resulting in prolonged control of virus infection and maintenance
of normal CD4 cell counts, even in the absence of further treatments.
The mechanisms by which such control is achieved and the implications
of such findings for the treatment and prevention of HIV infection
in human are being explored.
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