HTLV-1 infection of human retinal pigment epithelial cells and inhibition of viral infection by an antibody to ICAM-1.
OBJECTIVE
To examine whether human T-cell leukemia virus type 1 (HTLV-1) could infect a human retinal pigment epithelial (RPE) cell line, ARPE-19, in vitro and to investigate its regulation.


METHODS
A coculture system with ARPE-19 and irradiated cells of an HTLV-1-producing T-cell line, MT2 was used to determine the permissivity of RPE to HTLV-1 infection in vitro. The susceptibility to HTLV-1 was assessed by detection of viral DNA using the polymerase chain reaction (PCR), viral mRNA transcripts with reverse transcription PCR (RT-PCR) and viral antigen by immunofluorescence staining. An HTLV-1 Tax-activated HTLV-LTR-luciferase reporter assay was developed to measure viral infection quantitatively. The ICAM-1 expression on cocultured ARPE-19 cells was detected by flow cytometry and an ICAM-1-neutralizing antibody was used to test ICAM-1's role in the HTLV-1 infection of ARPE-19 cells. The regulation of HTLV-1 infection was investigated by culturing ARPE-19 cells with proinflammatory cytokines.


RESULTS
HTLV-1 infected ARPE-19 cells in vitro. The infection correlated with elevated expression of intercellular adhesion molecule (ICAM)-1 on the surface of ARPE-19 cells. ICAM-1-neutralizing antibody dramatically inhibited viral infection. Furthermore, proinflammatory cytokines dramatically suppressed HTLV-1 viral infection.


CONCLUSIONS
The tropism of HTLV-1 to retinal pigment epithelium could provide an explanation for the pathogenesis of HTLV-1-related ophthalmic diseases. A better understanding of specific roles of proinflammatory cytokines in the development of ophthalmic diseases may be beneficial for treatment.
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Baoying
B
Liu
Zhuqing
Z
Li
Sankaranarayana P
SP
Mahesh
Shree K
SK
Kurup
Chou-Zen
CZ
Giam
Robert B
RB
Nussenblatt
D019138:Antibodies, Blocking / Q000494:pharmacology*; D002460:Cell Line; D018920:Coculture Techniques; D016207:Cytokines / Q000494:pharmacology; D004279:DNA, Viral / Q000032:analysis; D005434:Flow Cytometry; D015967:Gene Expression Regulation, Viral / Q000502:physiology; D015486:HTLV-I Antigens / Q000378:metabolism; D015368:Human T-lymphotropic virus 1 / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology*; D010857:Pigment Epithelium of Eye / Q000187:drug effects / Q000378:metabolism / Q000821:virology*; D011533:Proviruses / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000821:virology; D014162:Transfection
D019138:Antibodies, Blocking; D016207:Cytokines; D004279:DNA, Viral; D015486:HTLV-I Antigens; D018799:Intercellular Adhesion Molecule-1