Treatment with a sphingosine analog does not alter the outcome of a persistent virus infection.
There is no known antiviral drug treatment that routinely terminates persistent virus infections. A recent provocative report indicated that low dosage of the sphingosine analog FTY720 caused lymphopenia in mice persistently infected with lymphocytic choriomeningitis virus (LCMV)-clone 13 (Cl 13) and induced viral clearance within 30 days post-treatment (Premenko-Lanier et al., 2008). However, we find that low dosage of FTY720 fails to purge LCMV-Cl 13 infection and does not induce lymphopenia in LCMV-Cl 13-infected mice. In fact, infection with non-persistent LCMV-Arm53b or with persistent LCMV-Cl 13 induces an equivalent lymphopenia, demonstrating that the quantity of circulating cells has little bearing on viral persistence. In addition, treatment with FTY720 or the sphingosine-1-phosphate receptor 1 (S1P1)-specific agonist, AUY954, does not alleviate T cell exhaustion and exacerbates disruption of the CD8(+) T cells response following LCMV-Cl 13 infection. Therefore, treatment with a sphingosine analog does not ameliorate persistent LCMV-Cl 13 infection.
Walsh
Kevin B
KB
Department of Immunology and Microbial Science, The Scripps Research Institute, IMM-6, TSRI, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Marsolais
David
D
Welch
Megan J
MJ
Rosen
Hugh
H
Oldstone
Michael B A
MB
D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D000068876:Fingolimod Hydrochloride; D008216:Lymphocytic Choriomeningitis / Q000188:drug therapy*; D008217:Lymphocytic choriomeningitis virus / Q000302:isolation & purification; D008231:Lymphopenia / Q000821:virology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011409:Propylene Glycols / Q000627:therapeutic use*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013876:Thiophenes / Q000627:therapeutic use; D016896:Treatment Outcome; D015091:beta-Alanine / Q000031:analogs & derivatives / Q000627:therapeutic use
C517408:AUY 954; D000998:Antiviral Agents; D011409:Propylene Glycols; D013876:Thiophenes; D015091:beta-Alanine; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine