Soluble Factors Secreted by Endothelial Cells Allow for Productive and Latent HIV-1 Infection in Resting CD4+T Cells.
In vitro, it is difficult to infect resting CD4+T cells with human immunodeficiency virus type 1 (HIV), but infections readily occur in vivo. Endothelial cells (ECs) interact with resting CD4+T cells in vivo, and we found previously that EC stimulation leads to productive and latent HIV infection of resting CD4+T cells. In this study, we further characterize the interactions between EC and resting T cells. We found that resting CD4+T cells did not require direct contact with EC for productive and/or latent infection to occur, indicating the involvement of soluble factors. Among 30 cytokines tested in a multiplex enzyme-linked immunosorbent assay (ELISA), we found that expressions for IL-6, IL-8, and CCL2 were much higher in EC-stimulated resting T cells than resting T cells cultured alone. IL-6 was found to be the soluble factor responsible for inducing productive infection of resting T cells, although direct contact with EC had an added effect. However, none of the cytokines tested, IL-6, IL-8, or CCL2, induced additional latent infection in resting T cells, suggesting that unidentified cytokines were involved. Intracellular molecules MURR1, c-Jun N-terminal kinase (JNK), and glucose transporter-1 (GLUT1) were previously shown in blocking HIV infection of resting CD4+T cells. We found that the concentrations of these proteins were not significantly different in resting T cells before and after stimulation by EC; therefore, they are not likely involved in EC stimulation of resting CD4+T cells, and a new mechanism is yet to be identified.
1 Department of Biology, Calvin College , Grand Rapids, Michigan.
John Henry
JH
Morris
1 Department of Biology, Calvin College , Grand Rapids, Michigan.
Tran
T
Nguyen
1 Department of Biology, Calvin College , Grand Rapids, Michigan.
Abuoma
A
Nwadike
1 Department of Biology, Calvin College , Grand Rapids, Michigan.
Mackenzie L
ML
Geels
1 Department of Biology, Calvin College , Grand Rapids, Michigan.
Derrick L
DL
Kamp
1 Department of Biology, Calvin College , Grand Rapids, Michigan.
Bo Ram
BR
Kim
2 Department of Pathology and Laboratory Medicine, University of Pennsylvania , Philadelphia, Pennsylvania.
Jean D
JD
Boyer
1 Department of Biology, Calvin College , Grand Rapids, Michigan.
Anding
A
Shen
D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000502:physiology / Q000821:virology*; D002450:Cell Communication; D016207:Cytokines / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism* / Q000502:physiology; D015497:HIV-1 / Q000254:growth & development*; D006801:Humans; D017735:Virus Latency
D016207:Cytokines
HIV; HIV/AIDS pathogenesis; T cells; viral reservoirs