TY - JOUR
T1 - Follicular dendritic cells and the persistence of HIV infectivity
T2 - The role of antibodies and Fcγ receptors
AU - Smith-Franklin, Beverly A.
AU - Keele, Brandon F.
AU - Tew, John G.
AU - Gartner, Suzanne
AU - Szakal, Andras K.
AU - Estes, Jacob D.
AU - Thacker, Tyler C.
AU - Burton, Gregory F.
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2002/3/1
Y1 - 2002/3/1
N2 - Large quantities of HIV are found trapped on the surface of follicular dendritic cells (FDCs), and virus persists on these cells until they ultimately die. We recently found that FDCs maintain HIV infectivity for long periods in vivo and in vitro. Because FDCs trap Ags (and virus) in the form of immune complexes and are rich in FcγRs, we reasoned that Ab and FcγRs may be required for FDC-mediated maintenance of HIV infectivity. To investigate this hypothesis, HIV immune complexes were formed in vitro and incubated for increasing times with or without FDCs, after which the remaining infectious virus was determined by HIV-p24 production in rescue cultures. FDCs maintained HIV infectivity in vitro in a dose-dependent manner but required the presence of specific Ab for this activity regardless of whether laboratory-adapted or primary X4 and R5 isolates were tested. In addition, Abs against either virally or host-encoded proteins on the virion permitted FDC-mediated maintenance of HIV infectivity. We found that the addition of FDCs to HIV immune complexes at the onset of culture gave optimal maintenance of infectivity. Moreover, blocking FDC-FcγRs or killing the FDCs dramatically reduced their ability to preserve virus infectivity. Finally, FDCs appeared to decrease the spontaneous release of HIV-1 gp120, suggesting that FDC-virus interactions stabilize the virus particle, thus contributing to the maintenance of infectivity. Therefore, optimal maintenance of HIV infectivity requires both Ab against particle-associated determinants and FDC-FcγRs.
AB - Large quantities of HIV are found trapped on the surface of follicular dendritic cells (FDCs), and virus persists on these cells until they ultimately die. We recently found that FDCs maintain HIV infectivity for long periods in vivo and in vitro. Because FDCs trap Ags (and virus) in the form of immune complexes and are rich in FcγRs, we reasoned that Ab and FcγRs may be required for FDC-mediated maintenance of HIV infectivity. To investigate this hypothesis, HIV immune complexes were formed in vitro and incubated for increasing times with or without FDCs, after which the remaining infectious virus was determined by HIV-p24 production in rescue cultures. FDCs maintained HIV infectivity in vitro in a dose-dependent manner but required the presence of specific Ab for this activity regardless of whether laboratory-adapted or primary X4 and R5 isolates were tested. In addition, Abs against either virally or host-encoded proteins on the virion permitted FDC-mediated maintenance of HIV infectivity. We found that the addition of FDCs to HIV immune complexes at the onset of culture gave optimal maintenance of infectivity. Moreover, blocking FDC-FcγRs or killing the FDCs dramatically reduced their ability to preserve virus infectivity. Finally, FDCs appeared to decrease the spontaneous release of HIV-1 gp120, suggesting that FDC-virus interactions stabilize the virus particle, thus contributing to the maintenance of infectivity. Therefore, optimal maintenance of HIV infectivity requires both Ab against particle-associated determinants and FDC-FcγRs.
UR - http://www.scopus.com/inward/record.url?scp=0036499181&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036499181&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.168.5.2408
DO - 10.4049/jimmunol.168.5.2408
M3 - Article
C2 - 11859132
AN - SCOPUS:0036499181
SN - 0022-1767
VL - 168
SP - 2408
EP - 2414
JO - Journal of Immunology
JF - Journal of Immunology
IS - 5
ER -