Hello All,

As the third EVER exiting scientist-member of the Lee clan, I would like to summarize my work and leave some perspectives on the project.

DC-SIGN is a C-type lectin receptor (CLR) and represents the famly of CLRs that serve as attachment factors for HIV. DC-SIGN binds to the glycoprotein gp120 of HIV with extremely high affinity and yet does not function to allow infection (liken to gp120's cognate receptor, CD4). What DC-SIGN does (and apparently what other members of CLRs do) is to bind HIV and transfer it to a truly infection permissive cell (such as T cells).

DC-SIGN is expressed mainly by dendritic cells (DC) and work in our lab has shown that DCs isolated from human rectal tissue can bind and transfer HIV much better than non-DC-SIGN cells derived from the same tissue (work of the first EVER exiting post-doc member, Kevin Gurney). Mutagenesis studies of DC-SIGN identified residues that affect binding to gp120 and work is in progress how we can utilize this to derive an inhibitor to block this interaction. Work is also in progress to identify residues on gp120 that reduce binding to DC-SIGN in hopes to derive antibodies using these gp120 mutants to block this interaction (see Patrick Hong's work).

The third area of research involves the molecular basis of the binding and transfer of HIV to permissive cells. Namely, there are threee ways DC-SIGN can transfer HIV to permissive cells. One, HIV can be transferred by merely physically being on the cell surface and contact with a CD4+ cell will initiate transfer and infection. Secondly, HIV bound on DC-SIGN can transfer HIV to resident CD4 molecules on DCs and initiate infection of DCs. This way, de novo and newly made virions can now be transferred to and infect a CD4+ cell. Thirdly, incoming HIV bound to DC-SIGN or any CLRs can be internalized and recycled back to the cell surface until a CD4+ cell comes in contact with the DCs to allow for infection. This is a novel mechanism that HIV may use to maintain a reservoir of virions until the time comes for it to infect a CD4+ cell. We are currently seeking to purify intracellular proteins that mediate this process.




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