Related Experiment Videos
Complement dependent trapping of infectious HIV in human lymphoid tissues
Zoltán Bánki1, Laco Kacani, Peter Rusert
1Department of Hygiene, Microbiology and Social Medicine, Innsbruck Medical University and Ludwig-Boltzmann-Institute for AIDS Research, 6020 Innsbruck, Austria.
AIDS (London, England)
|March 15, 2005
Summary
Infectious HIV is trapped in germinal centers (GC) by follicular dendritic cells (FDC) via complement receptor 2 (CR2). Targeting this viral reservoir could be a new HIV therapy strategy.
Area of Science:
- Immunology
- Virology
- Infectious Diseases
Background:
- Extracellular HIV-1 bound to follicular dendritic cells (FDC) in germinal centers (GC) constitutes the largest viral reservoir in individuals with HIV.
- The infectivity of HIV trapped within human GC has not been directly established.
- Complement receptors and Fc gamma receptors are hypothesized to mediate HIV trapping in GC.
Purpose of the Study:
- To investigate the roles of complement and Fc gamma receptors in binding HIV to lymphoid tissues (LT).
- To assess the infectivity of HIV trapped in human GC.
Main Methods:
- HIV was detached from LT of HIV-positive individuals using antibodies that block complement and Fc gamma receptors.
- Detached HIV was quantified using HIV p24 ELISA and PCR.
- Viral infectivity was assessed through in vitro assays.
- The presence and accessibility of viral envelope proteins, complement factors, and immunoglobulins on detached viral particles were evaluated.
Main Results:
- Both C3d fragments and IgG molecules were found on detached HIV.
- HIV trapping was mediated exclusively by CR2-C3d interactions; Fc gamma receptors played no detectable role.
- Infectivity assays revealed that HIV particles from 4 out of 10 patients remained infectious.
Conclusions:
- Infectious HIV is trapped in GC by CR2-expressing FDC (or B cells).
- Reducing this HIV pool represents a potential therapeutic target for HIV infection.