The Ctype lectin surface receptor DCIR contributes to trans and cis infection pathways

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The C-type lectin surface receptor DCIR
contributes to trans- and cis- infection pathways
Alexandra Lambert, MSc
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Dendritic cells (DC) play an important role in
primo-infection

• Capture HIV-1 by their dendrites
• DC are susceptible to infection but less than CD4
• Permit transport of HIV-1 to lymph nodes hidden
  from immune system

Lumen of vagina
Cervicovaginal epithelium
Submucosal epithelium
Pope M. IAVI 2004
Brenchley et al J. Exp Med 2004
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Dendritic cell transmit HIV-1 to T cells by two
mechanisms

• Transfer of HIV-1 after de novo virus production
  cis-infection

Virion
Viral DNA
Dendritic cells
De novo HIV-1 production
Late transfer or cis-infection
CD4 T cells
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Dendritic cells transmit HIV-1 to T cells by two
mechanisms

• Transfer of HIV-1 without de novo virus
  production trans-infection

• Attachment receptors
• C-type lectin receptors (DC-SIGN, mannose
  receptor, etc)
• Syndecan 3
• Other

Virion
CCR5
CD4
Early transfer or trans-infection
Dendritic cells
CD4 T cells

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C-type lectin receptor family
Figdor C. G. et al, 2002 Nat. Rev. Immunol
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What is DCIR?

• DCIR Dendritic Cell Immuno Receptor
• It is a member of C-type lectin receptor family
  but little is known about the function of this
  receptor because there are few studies about it
  (Bates et al J. Immunol 1999)
• It is found on the surface of B cells, monocytes,
  macrophages, neutrophiles (Bates et al J. Immunol
  1999) and also found on CD4 T cell in arthritis
  patients (Eklöw et al Ann Rheum Dis 2008)
• No ligand identified yet

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HIV-1 exploits DCIR to bind to DC and to be
transferred to CD4 T cell
Decrease of 30 of transfer
Lambert A.A et al., 2008 Blood
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DCIR is involved in trans-infection
Donor 1
Donor 2
0
EFA X
Trans-infection or Early transfer
Lambert A.A et al., 2008 Blood
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DCIR is involved in cis-infection
Significative descrease of the amount of
transferred virus
Lambert A.A et al., 2008 Blood
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DCIR is involved in productive infection
In DC
In Raji CD4
Infection with de novo production
Lambert A.A et al., 2008 Blood
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Importance of the DCIR neck domain for HIV-1
binding
Lambert A.A et al., 2008 Blood
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Importance of the neck domain for virus infection
DCIR wild type
DCIR ? neck
Lambert A.A et al., 2008 Blood
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Summary of findings

• HIV-1 can use DCIR as an attachment factor on the
  surface of DC
• DCIR participates to productive infection of DC
  and DC-mediated virus transfer to CD4 T cells
• Neck domain of DCIR is important for virus
  binding and infection

Lambert A. A, Gilbert C, Tremblay M.J. The C-type
lectin surface receptor DCIR acts as a new
attachment factor for HIV-1-1 in dendritic cells
and contributes to trans- and cis-infection
pathways. 2008, Blood, Epub ahead of print
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Acknowledgments
Michel J. Tremblay (my supervisor) Caroline
Gilbert (my co-supervior) All members of the
Michel J. Tremblays Lab
CIHR Doctoral Award and Operating grant
(MOP-79542) - HIV-1/AIDS Research Program