Retention of antigen on follicular dendritic cells and B lymphocytes through complement-mediated multivalent ligand-receptor interactions: theory and application to HIV treatment.
In HIV-infected patients, large quantities of HIV are associated with follicular dendritic cells (FDCs) in lymphoid tissue. During antiretroviral therapy, most of this virus disappears after six months of treatment, suggesting that FDC-associated virus has little influence on the eventual outcome of long-term therapy. However, a recent theoretical study using a stochastic model for the interaction of HIV with FDCs indicated that some virus may be retained on FDCs for years, where it can potentially reignite infection if treatment is interrupted. In that study, an approximate expression was used to estimate the time an individual virion remains on FDCs during therapy. Here, we determine the conditions under which this approximation is valid, and we develop expressions for the time a virion spends in any bound state and for the effect of rebinding on retention. We find that rebinding, which is influenced by diffusion, may play a major role in retention of HIV on FDCs. We also consider the possibility that HIV is retained on B cells during therapy, which like FDCs also interact with HIV. We find that virus associated with B cells is unlikely to persist during therapy.
Hlavacek
William S
WS
Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USA. wish@lanl.gov
Percus
Jerome K
JK
Percus
Ora E
OE
Perelson
Alan S
AS
Wofsy
Carla
C
D019380:Anti-HIV Agents / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000276:immunology*; D003165:Complement System Proteins / Q000276:immunology* / Q000378:metabolism; D020566:Dendritic Cells, Follicular / Q000276:immunology*; D015488:HIV Antigens / Q000276:immunology*; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1 / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D018448:Models, Immunological; D017464:Receptors, Complement 3d / Q000276:immunology / Q000378:metabolism
D019380:Anti-HIV Agents; D015488:HIV Antigens; D017464:Receptors, Complement 3d; D003165:Complement System Proteins