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.
Liu
Baoying
B
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Li
Zhuqing
Z
Mahesh
Sankaranarayana P
SP
Kurup
Shree K
SK
Giam
Chou-Zen
CZ
Nussenblatt
Robert B
RB
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