Experimental Studies On The Influence Of Allitridin On Viral Load In MCMV Infected Mice

Objectives:①To study the treatment effects of allitridin against murine cytomegalovirus (MCMV) infection in vivo;②To explore the dynamic change of virus load in internal organs of MCMV infected mice;③To evaluate the influence of allitridin on the virus load in internal organs of MCMV infected mice.Methods:①The establishment of MCMV infected mice model: After the proliferation of MCMV Smith strain, MCMV systemically disseminated infected mice model of non-immunosuppressive was established by using BALB/c mice of 4.5 weeks old and without using immunosuppressant.②The determination of the therapeutic dose of allitridin: According to the medium dosage of allitridin for human adults was 120mg/kg·d, the medium dose for mice was 25mg/ kg·d.③Grouping and the time of detection: 60 MCMV infected mice were randomly allocated into two groups, placebo-treated group and allitridin-treated group. The therapy started at 24 hours after the inoculation of viruses and this time point was defined as 0d. The mice were sacrificed for collection of salivary gland, liver, spleen and kidney at 1d, 3d, 7d, 14d, 28d, 45d, 60d, 75d, 90d and 120d, respectively.④The relative amount of MCMV DNA in liver, spleen, kidney and salivary gland of placebo-treated group and allitridin-treated group was detected by real time PCR method.Results:①The dynamic change of MCMV DNA in liver of MCMV infected mice: MCMV DNA was detected in liver on day 1, and reached the peak on day 14, then began to descend and reached relative low level on day 28, and continuously decreased slowly, till day 120.②The dynamic change of MCMV DNA in spleen of MCMV infected mice: MCMV DNA was detected in spleen on day 3, and reached the peak on day 14, then began to descend and reached relative low level on day 28, and subsequently descended gradually, till day 120.③The dynamic change of MCMV DNA in kidney of MCMV infected mice: MCMV DNA was detected in kidney on day 3, and reached the peak on day 14, then began to descend and reached relative low level on day 28, and subsequently descended slowly, till day 120.④The dynamic change of MCMV DNA in salivary gland of MCMV infected mice: MCMV DNA was detected in salivary gland on day 1, and reached the peak on day 28, then began to descend to relative high level on day 45, then subsequently kept on this level, till to day 120.⑤The dynamic change of MCMV DNA in liver of allitridin-treated mice: MCMV DNA was detected in liver of allitridin-treated mice on day 1, and subsequently increased gradually, and reached the peak on day 7, then began to decline. The level of MCMV DNA of allitridin-treated mice was obviously lower than that of MCMV infected group on day 14, and there was no significant difference between them after day 28.⑥The dynamic change of MCMV DNA in spleen of allitridin-treated mice: MCMV DNA was detected in spleen of allitridin-treated mice on day 7. MCMV DNA level of drug-treated group was obviously lower than that of MCMV infected group on day 7, 14 and 28, then subsequently descended gradually, and there was no significant difference between two groups after day 28.⑦The dynamic change of MCMV DNA in kidney of allitridin-treated mice: MCMV DNA was detected in kidney of allitridin-treated mice on day 3, then subsequently increased gradually, and reached the peak on day 14. The MCMV DNA level of allitridin-treated group was obviously lower than that of MCMV infected group on day 14, then descended slowly, and there was no significant difference between two groups after day 14.⑧The dynamic change of MCMV DNA in salivary gland of allitridin-treated mice: MCMV DNA was detected in salivary gland of allitridin-treated mice on day 1, then subsequently increased gradually, and reached the peak on day 28, then began to decline, but remained relative high level, and kept on the level till to day 120. MCMV DNA level of allitridin-treated group was obviously lower than that of MCMV infected mice on day 7, 14 and 28.Conclusions:①It appeared the mode that viral load increased quickly and then quickly descended in main prone organ of MCMV infected mice model in acute phase. While in chronic phase, viral load was in a low level and descended slowly, which indicated mice could inhibit viral replication efficiently by establishing specific viral immunity, however, it couldn't clear virus completely.②Applying allitrdin treated mice model, it was found that allitrdin could lower viral load markedly when virus proliferation was in peak in acute infection phase. However, when virus reproduction kept in a low level in chronic infection phase, allitridin had not obvious influence on the viral load.