Cell-free HTLV-1 infects dendritic cells
Cell-free HTLV-1 infects dendritic cells leading to transmission and transformation of CD4(+) T cells.
Human T-lymphotropic virus type I (HTLV-1) is a human retrovirus that can cause both a type of leukemia and a progressive neurological disorder, and many HTLV-1-infected individuals have weakened immune systems. For many years, studies of how this virus is transmitted have been hampered by the fact that, unlike other retroviruses including HIV, HTLV-1 viral particles do not infect their primary target cells, CD4+ T cells, in vitro. Recently, work in the laboratory of Frank Ruscetti has revealed that HTLV-1 viral particles can efficiently infect another type of immune cell called dendritic cells (DC) in vitro. They observed that both myeloid and plasmacytoid DC can be infected, and that the virus produced by DC can be used to infect other DC.
Moreover, they observed that, after being exposed to HTLV-1, DC can rapidly transfer the virus to CD4+ T cells. In contrast to what happens after exposure to cell-free virus particles, CD4+ T cells exposed to HTLV-1 via DC are efficiently infected with the virus. This infection also results in transformation of the CD4+ T cells, generating immortalized cells that are very similar to the leukemic cells in HTLV-1-infected individuals. Studies of cells isolated from an HTLV-1-infected individual revealed that DC were infected, produced virus, and could infect T cells. Since these studies reveal that DC can be infected by cell-free virus and that T cells can be efficiently infected via DC, they indicate that the current paradigm of HTLV-1 infection, which involves cell-cell transmission of the virus between T cells, should be reconsidered. In addition, these studies suggest that impairment of DC function following HTLV-1 infection plays a role in pathogenesis.
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Frank W. Ruscetti Web Site
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