Reinhard Research Provides Insights into HIV-1
Professor Bjoern Reinhard
Recently reported in PNAS, Bjoern Reinhard and his collaborator at the BU Medical School, Dr. Suryaram Gummuluru, have confirmed a unique HIV-1 DC attachment mechanism using lipoparticles with defined surface composition. The mechanism is dependent on a host-cell–derived ligand, GM3, and is a unique example of pathogen mimicry of host-cell recognition pathways that drive virus capture and dissemination in vivo. These insights provide the basis for the development of artificial virus nanoparticles with host-derived surface groups that inhibit the HIV-1 trans-dissemination pathway through dendritic cells. The virus parasite uses these dendritic cells to facilitate its dissemination, while avoiding recognition.
Citation: Puryear, et al., “HIV-1 incorporation of host-cell–derived glycosphingolipid GM3 allows for captureby mature dendritic cells”, Proc Natl Acad USA, 2012, 109 (19), 7475-7480.
Gangliosides with α2–3 NeuNAc linkages are important for HIV-1 capture by mDCs. (A) Gag-eGFP VLPs were mock treated or treated with 0.5 units/μL α2–3, 2–6, 2–8 NA. (B) Gag-eGFP VLPs were derived from siRNA-treated HEK293T cells. NT, nontargeting; UGT8, galactosyl transferase; CERT, ceramide transfer protein; UGCG, glucosyltransferases, ST3, GM3 transferase. Capture of VLPs by mDCs was analyzed by FACS (A and B). Data are reported as percentage of eGFP+ mDCs normalized to NT-treated VLPs. (C and D) Ganglioside-deficient HIVLai was derived from HEK293T cells knocked down for NT, UGCG, or ST3. (C) Virions were labeled for p24gag (green) and GM3 (red). Representative fields are shown and the average mean fluorescent intensity (MFI) of GM3 normalized to p24gag ± SD is reported, *P < 0.001, one-way ANOVA with Dunnett’s multiple comparison. (D) Fold decrease of ganglioside-depleted HIVLai capture relative to NT-treated viruses by mDCs is reported. (E) Fold decrease in HIVLaiΔEnv virus capture treated with 0.5 units/μL α2–3, 2–6, 2–8 NA or α2–3-specific NA relative to mock-treated viruses by mDCs is reported. All capture assays represent averaged data from a minimum of three donors, ±SEM, one-sample t test, *P < 0.05, **P < 0.01, ***P < 0.001.