Effects of tacrolimus on infection of Friend murine leukemia virus to Fv-4 gene heterozygous mice.
OBJECTIVE
To investigate the effect of tacrolimus (FK506) on the infection of Friend murine leukemia virus (Friend MuLV) in vivo.


METHODS
Three kinds of mice were used including Friend MuLV-sensitive BALB/c mice, Friend MuLV-resistant Fv-4 gene-homozygous mice (Fv-4 mice), and Friend MuLV-resistant Fv-4 gene-heterozygous mice (F1 mice). Tacrolimus was administrated i.p. to those mice in every 2 d. Those treated mice were inoculated i.p. with Friend MuLV once on d 3. The symptoms and viral proliferations in those mice were observed to recognize the Friend MuLV infection. The expression and genotype of Fv-4 gene that resistant against the infection of Friend MuLV were analyzed to confirm the genomic background and related mechanism of the resistance.


RESULTS
BALB/c mice and F1 mice, but not Fv-4 mice, appeared obvious early death, spleenomegaly, and viral proliferation after both treatments of viral inoculation and tacrolimus administration, whereas the expression and genotype of Fv-4 gene was not changed in F1 mice and Fv-4 mice with treatment of tacrolimus. Compared to the virus-inoculated control, the Friend MuLV-sensitivity of tacrolimus-treated BALB/c mice and the Friend MuLV-resistance of tacrolimus-treated Fv-4 mice were the same as the controls, but only F1 mice became the symptoms and viral proliferation after both treatments. It suggested the Friend MuLV-resistant F1 mice could be converted to be Friend MuLV-sensitive by treatment of tacrolimus, and this conversion was not depended on the expression and genotype of Fv-4 gene.


CONCLUSIONS
Tacrolimus could not inhibit the infection of Friend MuLV in all mice, furthermore, it could enhance the infection of Friend MuLV in F1 mice. The enhancement may be related to the immunosuppressive effect of tacrolimus.
Zhang
Feng-min
FM
Department of Microbiology, Harbin Medical University, Harbin 150086, China. zhangfm@ems.hrbmu.edu.cn
Yang
Bao-feng
BF
Gu
Hong-xi
HX
Chen
Xiao-bei
XB
Zhong
Zhao-hua
ZH
Cheng
Zhi
Z
D000818:Animals; D005622:Friend murine leukemia virus / Q000254:growth & development*; D020022:Genetic Predisposition to Disease; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007942:Leukemia, Experimental / Q000821:virology; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D012192:Retroviridae Infections / Q000821:virology; D013154:Spleen / Q000378:metabolism* / Q000473:pathology; D016559:Tacrolimus / Q000494:pharmacology*; D014412:Tumor Virus Infections / Q000821:virology; D014779:Virus Replication / Q000187:drug effects
C103555:Fv4 protein, mouse; D007166:Immunosuppressive Agents; D008565:Membrane Proteins; D016559:Tacrolimus