Distinct Intracellular Trafficking Patterns of Host IgG by Herpes Virus Fc-Receptors
Abstract
Members of both alpha and beta herpes viruses affects 50–98% of people around the world. They cause severe symptoms in congenitally infected newborns, a lifelong latent infection that is lethal in immunocompromised individuals, and are associated with several types of cancer. Human cytomegalovirus (HCMV) and herpes simplex virus type 1 (HSV-1) viruses express proteins (HCMV gp68 and gp34; HSV-1 gE-gI) that function as Fc receptors (FcRs) by binding to the Fc regions of human IgG. In addition to binding free IgG, these viral FcRs can bind to IgG complexed with an antigen to form an antibody bipolar bridged (ABB) complex. Although HCMV gp68 and HSV-1 gE-gI have an overlapping binding site on Fc, the finding that the gp68/Fc interaction is stable at pH values between 5.6 and 8.1 but that gE-gI binds only at neutral or basic pH suggests distinct pH-based downstream events after IgG is internalized via receptor-mediated endocytosis into intracellular compartments. Here we developed a cell-based in vitro model system to define the fates of ABB complexes formed by the two types of viral FcRs. We found that alpha (HSV-1) and beta (HCMV) herpes virus FcRs displayed distinct intracellular trafficking patterns to target internalized ligands: HSV-1 gE-gI dissociates from its IgG-antigen ligand in acidic endosomal compartments and recycles back to the cell surface, whereas HCMV FcRs (gp68) are transported together with IgG-antigen complexes to lysosomes for degradation. In both cases, anti-viral IgGs and their viral targets are selectively degraded, a potential immune evasion strategy allowing herpes viruses to escape from IgG-mediated immune responses.
Additional Information
© American Society for Cell Biology. POSTER PRESENTATIONS- Sunday, December 7.Attached Files
Published - Ndjamen_2014pP1217.pdf
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- Eprint ID
- 57200
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- CaltechAUTHORS:20150504-125103596
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2015-05-06Created from EPrint's datestamp field
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2019-10-03Created from EPrint's last_modified field