HTLV type IIIB infection of human thymic epithelial cells: viral expression correlates with the induction of NF-kappa B-binding activity in cells activated by cell adhesion.
Productive infection by the LAV strain has been demonstrated in T cell precursors at different stages of intrathymic development, while viral replication in thymic epithelial cells is still controversial. In this article we show that epithelial cell cultures derived from the medullary component of normal thymus are infectable by HTLV-IIIB virus through cell-free and lymphoid-mediated transmission. Free virus inoculum results in the integration of proviral copies undergoing poor replication, whereas lymphoid-mediated transmission leads to substantial viral expression and the production of viral progeny able to secondary infect lymphoid cells. Interleukin 6 production and phenotype changes (increased expression of MHC class I and ICAM-1) were induced in TE cells by contact with free virus or by adhesion to infected lymphoid cells. By contrast, NF-kappa B-binding activity on the HIV-1 LTR kappa B enhancer element was upregulated only by contact with infected lymphoid cells, but not with virus. The viral replication observed in TE cells after lymphoid-mediated transmission correlates with the upregulation of NF-kappa B-binding activity. Interleukin 6 increased production and phenotype changes and increased NF-kappa B-binding activity were also induced by adhesion to uninfected lymphoid cells, demonstrating that lymphoepithelial cell contacts can activate TE cells. These results demonstrate that thymic epithelial cells are permissive to HIV infection and that viral replication in this cell lineage can be modulated by intracellular signals delivered by adhesive contacts.
Ramarli
D
D
Instituto di Immunologia e Malattie Infettive, Università di Verona, Italy.
Reina
S
S
Merola
M
M
Scupoli
M T
MT
Poffe
O
O
Riviera
A P
AP
Brentegani
M
M
Fiorini
E
E
Vella
A
A
Varnier
O
O
Tridente
G
G
D002448:Cell Adhesion; D002460:Cell Line; D002675:Child, Preschool; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D010641:Phenotype; D013950:Thymus Gland / Q000166:cytology / Q000378:metabolism* / Q000821:virology
D015850:Interleukin-6; D016328:NF-kappa B