Large amounts of HIV are trapped on follicular dendritic cells (FDC) in the germinal centers of secondary lymphoid tissues. throughout clinical latency when CD+4 T cells continually decline, these germinal centers with virus-laden FDC, highly activated, CD+4 T cells and a state of high cellular activation are the primary sites of active HIV replication. The investigators hypothesize that FDC play a major role in HIv pathogenesis by: (1) serving as a reservoir of infectious HIV; (2) potentiating both de novo infection of newly entering cells and of latently infected cells coming into the germinal center; and (3) by permitting infection in the presence of high levels of neutralizing antibody. They also hypothesize that FDC features that promote infection may be able to be inhibited. In support of the hypothesis, they have recently shown that FDC trapped HIV immune complexes are highly infectious and they have data suggesting that FDC maintain HIV infectivity even in the absence of viral replication. They also have evidence that FDC promote a significant increase in the amount of HIV infection in both newly and latently infected T cells. Lastly they have found that FDC permit infection even in the presence of a vast excess of neutralizing antibody. The investigators believe that their hypothesis is exciting and that an understanding of FDC contributions to HIV pathogenesis will be critical in designing intervention strategies that can attack this reservoir of infectious virus. Current strategies to stop viral replication do not target the FDC reservoir which remains until the cells are destroyed and the lymph node involutes prior to the onset of AIDS. thus an understanding of FDC contributions may allow them to successfully target this important cell and its viral reservoir.
| Zhou, Xueyuan; Shapiro, Leland; Fellingham, Gilbert et al. (2011) HIV replication in CD4+ T lymphocytes in the presence and absence of follicular dendritic cells: inhibition of replication mediated by ?-1-antitrypsin through altered I?B? ubiquitination. J Immunol 186:3148-55 |
| Thacker, Tyler C; Zhou, Xueyuan; Estes, Jacob D et al. (2009) Follicular dendritic cells and human immunodeficiency virus type 1 transcription in CD4+ T cells. J Virol 83:150-8 |
