| Abstract |
With a background of NIH-supported studies
on B-cell lymphomas, this research represents a pilot study
in HIV/AIDS for this investigator. Although B lymphocytes
are a major constituents of lymphoid organs and acquire a
significant altered phenotype and function in HIV-infected
individuals, it remains unclear whether mostly CD4-negative
B cells are susceptible fot viral entry and long term productive
infection. This issue is of significance in the context of
HIV-1 infection which is associated with both cellular and
humoral deficiencies. During HIV infection, B cell disorders
including polyclonal activation, hypergammaglobulinemia, and,
most importantly, high-grade B cell lymphomas, occur frequently
and result in humoral immunodeficiency. Although in vitro
HIV-1 infection of B cells and cell surface trapping of HIV-1
by B cell CD21 receptor have been recently documented, the
process of HIV-1 infection of B cells needs further clarification,
in the context of long term productive infection, CD4-independent
chemokine receptor usag , preference for naive or memory B
cells, and oncogenic consequences.
Dr. Sharma's research objective has been to characterize
B cell-derived HIV-1strains for genetic and functional alterations,
establish ex-vivo HIV-1 infection of B cells using human tonsil
explant infection system, assess the frequency of in vivo
infected B cells in peripheral blood samples from HIV infected
patients, and establish a possible link between the unintegrated
viral genome and productive infection. Using CD4-negative
Burkitt's lymphoma cell lines and normal naive and germinal
center/memory tonsillar B cells, Dr. Sharma has recently demonstrated
that HIV-1 strains can productively infect B cells in a CD4
independent but CXCR4 dependent manner. Furthermore, B cell-derived
virus was found to be capable of infecting T cells and of
inducing activation markers in B cells. A B cell clone derived
from HIV-1-infected B cell line has been maintained for over
36 months with active HIV production. The viral genome in
this clone predominantly exists in unintegrated linear and
circular forms. This is inconsistent with the concept that
a productive infection by HIV-1 is strictly a result of integrated
proviruses. Dr. Sharma's HIV-related NIH funding is pending
(R01 CA83517).
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