Cell-free HTLV-1 infects dendritic cells leading to transmission and transformation of CD4(+) T cells.
Cell-free human T-lymphotropic virus type 1 (HTLV-1) virions are poorly infectious in vitro for their primary target cells, CD4(+) T cells. Here, we show that HTLV-1 can efficiently infect myeloid and plasmacytoid dendritic cells (DCs). Moreover, DCs exposed to HTLV-1, both before and after being productively infected, can rapidly, efficiently and reproducibly transfer virus to autologous primary CD4(+) T cells. This DC-mediated transfer of HTLV-1 involves heparan sulfate proteoglycans and neuropilin-1 and results in long-term productive infection and interleukin-2-independent transformation of the CD4(+) T cells. These studies, along with observations of HTLV-1-infected DCs in the peripheral blood of infected individuals, indicate that DCs have a central role in HTLV-1 transmission, dissemination and persistence in vivo. In addition to altering the current paradigm concerning how HTLV-1 transmission occurs, these studies suggest that impairment of DC function after HTLV-1 infection plays a part in pathogenesis.
Jones
Kathryn S
KS
Basic Research Program, Science Applications International Corporation-Frederick, Frederick, Maryland 21702, USA. joneska@mail.nih.gov
Petrow-Sadowski
Cari
C
Huang
Ying K
YK
Bertolette
Daniel C
DC
Ruscetti
Francis W
FW
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D002450:Cell Communication; D002460:Cell Line; D002472:Cell Transformation, Viral; D002474:Cell-Free System; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology*; D015490:HTLV-I Infections / Q000276:immunology / Q000635:transmission / Q000821:virology; D019812:Heparan Sulfate Proteoglycans / Q000276:immunology; D015368:Human T-lymphotropic virus 1 / Q000276:immunology / Q000472:pathogenicity*; D006801:Humans; D020104:Immunophilins / Q000276:immunology; D066298:In Vitro Techniques; D008213:Lymphocyte Activation
D019812:Heparan Sulfate Proteoglycans; D020104:Immunophilins