Role for CD21 in the establishment of an extracellular HIV reservoir in lymphoid tissues.
Follicular dendritic cells (FDC) represent a major extracellular reservoir for HIV. A better understanding of the mechanisms of virion attachment to FDC may offer new avenues for reducing viral burdens in infected individuals. We used a murine model to investigate the establishment of extracellular HIV reservoirs in lymph nodes (LN). Consistent with findings in human tissues, CD21 was required for trapping of HIV to LN cells, as evidenced by significantly reduced virion binding when mice were pretreated with a C3 ligand-blocking anti-CD21 mAb and absence of virion trapping in CD21 knockout mice. Also consistent with findings in human tissues, the majority of HIV virions were associated with the FDC-enriched fraction of LN cell preparations. Somewhat surprisingly, HIV-specific Abs were not essential for HIV binding to LN cells, indicating that seeding of the FDC reservoir may begin shortly after infection and before the development of HIV-specific Abs. Finally, the virion-displacing potential for anti-CD21 mAbs was investigated. Treatment of mice with anti-CD21 mAbs several days after injection of HIV significantly reduced HIV bound to LN cells. Our findings demonstrate a critical role for CD21 in HIV trapping by LN cells and suggest a new therapeutic avenue for reducing HIV reservoirs.
Ho
Jason
J
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Moir
Susan
S
Kulik
Liudmila
L
Malaspina
Angela
A
Donoghue
Eileen T
ET
Miller
Natalie J
NJ
Wang
Wei
W
Chun
Tae-Wook
TW
Fauci
Anthony S
AS
Holers
V Michael
VM
D000818:Animals; D019138:Antibodies, Blocking / Q000378:metabolism; D001666:Binding Sites, Antibody; D020566:Dendritic Cells, Follicular / Q000276:immunology / Q000378:metabolism / Q000821:virology; D005110:Extracellular Space / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D006678:HIV / Q000276:immunology / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D006801:Humans; D020014:K562 Cells; D008221:Lymphoid Tissue / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017464:Receptors, Complement 3d / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D015728:Receptors, HIV / Q000037:antagonists & inhibitors / Q000378:metabolism; D014771:Virion / Q000276:immunology / Q000378:metabolism
D019138:Antibodies, Blocking; D017464:Receptors, Complement 3d; D015728:Receptors, HIV