• Rakela, Jorge (PI)

Project: Research project

Project Details


DESCRIPTION: (Applicant's Abstract)
Hepatitis C virus (HCV) coinfection is common in human immunodeficiency virus
type I (HIV-1) infected subjects. Epidemiological data suggest that in HIV-1
and HCV coinfected patients, HCV infection is more severe and progression to
AIDS is more rapid. Furthermore, HIV infection was reported to facilitate
mother-to-infant transmission of HCV and also HCV infection was reported to
facilitate mother-to-infant transmission of HIV. Our overall hypothesis is that
HCV replicates in lymphoid cells and that this phenomenon is responsible for
the observed interactions between HIV-1 and HCV infections. Using
strand-specific assays, we have demonstrated the presence of HCV RNA negative
strand, which is a viral replicative intermediary, in multiple extrahepatic
sites, but particularly common in lymphoid tissue. This infection was mainly
localized in monocyte/macrophage cells. Moreover, we found that viral sequences
at extrahepatic replication sites commonly differ from circulating and
liver-derived sequences. Our proposal aims to further characterize extrahepatic
HCV replication among HIV-1-infected subjects. Furthermore, we will analyze the
presence of HCV replication in peripheral blood mononuclear cells (PBMCs) and
cervical lavage cells in a large group of HIV-1-positive mothers and we will
correlate these data with transmission of HCV and HIV-1 into children. To
determine whether macrophage-derived HCV strains are responsible for viral
transmission into children, we will analyze viral quasispecies composition in
serum and PBMCs from mothers and children and in cervical lavage cells from
mothers. We will also determine whether HCV infection of antigen presenting
cells affects their function. Accordingly, we will culture dendritic cells from
HCV-infected and uninfected individuals and compare them in functional assays
in vitro. In summary, our studies will further characterize extrahepatic
replication of HCV in HIV-1 infected subjects and will elucidate its role in
mother-to-infant transmission of these two viruses.
Effective start/end date9/30/008/31/04


  • Medicine(all)


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