Background: Human parechovirus type 3 (HPeV3) is an emerging pathogen causing sepsis and meningoencephalitis in neonates and young infants. Specific treatment for HPeV3-related severe diseases is currently unavailable. Our previous studies indicated that 1) maternal antibodies to HPeV3 has an important role to protect neonates and young infants from HPeV3-related diseases, and 2) commercially available intravenous immunoglobulin (IVIG) contains high antibody titers of human parechoviruses (HPeVs) including HPeV3. We hypothesized that IVIG suppresses HPeV3 RNA levels in an in vitro model.
Methods: We used LLC-MK2 cells infected with HPeV3, which were treated with either the mean peak steady-state levels in human plasma during IVIG therapy (Cmax: 10 mg/mL) or a lower dose (0.1 mg/mL) on day 0 (simultaneously with HPeV3 exposure) or day 1 (24 hours after HPeV3 exposure). The infected cells were incubated for 7 days at 37ºC in 5% CO2. Both extracellular (EC) and intracellular (IC) levels of HPeVs RNA were measured by real-time PCR on days 0, 1, 3, 5 and 7.
Results: When the cells were untreated, IC and EC levels of HPeV3 RNA increased to 4.71X106 and 5.69X107 copies/µL on day 7, respectively. When the cells were treated with Cmax of IVIG on day 0, IC and EC levels of HPeV3 RNA at every observational period were continuously suppressed (Figure). On day 7, IC and EC levels of HPeV3 RNA were decreased to 2.83X103 and 2.97X102 copies/µL, respectively (Figure). When the cells were treated with a lower dose, the suppression of HPeV3 RNA levels was less than that of cells treated with Cmax, demonstrating a dose-dependent effect. When the treatment with Cmax of IVIG was performed on day 1, IC and EC levels of HPeV3 RNA on day 7 were suppressed 1.12X105 and 7.82X103 copies/µL, respectively; however, the suppression of the HPeV3 RNA levels was less than those of cells treated on day 0. A similar dose-dependent effect was also observed when the cells were treated on day 1 with a lower dose.
Conclusion: IVIG suppressed IC and EC levels of HPeV3 RNA in an in vitro model in a dose-dependent manner. Additionally, administration of IVIG at earlier time point suppressed HPeV3 RNA levels more efficiently. Thus, IVIG treatment may be a potential candidate for neonates and young infants with HPeV3-related severe diseases.
K. Watanabe, None
A. Saitoh, None
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