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Human cytomegalovirus (HCMV) is an opportunistic pathogen that causes severe diseases in congenitally infected newborns and immunocompromised patients. Currently, no vaccine is available to prevent HCMV infection. Anti-viral drugs are limited by their side effects and drug resistance. In this study, by performing a medium-sized, anti-HCMV chemical screening, we identified SP600125, CC-401, and the c-Jun N-terminal kinase (JNK) inhibitor VIII, three structurally different small molecule JNK inhibitors that effectively inhibited HCMV replication in cultured human fibroblasts (HFs). SP600125 showed its potential by inhibiting the viral replication of a HCMV laboratory strain in HFs and a HCMV clinical strain in human retinal pigment epithelial cells. Knockdown of JNK expression by RNA interference significantly impaired HCMV replication, mimicking the effect of the chemical inhibitors on virus infection. Mechanistically, SP600125 affects a very early step of the viral life cycle. Viral binding, entry, and the delivery of viral DNA into the cells were not inhibited by the compound. Instead, it suppressed the transcription of the immediate-early viral genes IE1/2 and the accumulation of their gene products. IE1/2 are among the first genes expressed after viral entry, and they are the master regulators of late phase viral gene expression. Consistent with this notion, the expression of other viral genes was also reduced after SP600125 treatment. We propose that JNK inhibitors have the potential to become a new class of anti-HCMV drug candidates, and JNK is a feasible target for the development of anti-HCMV drugs., (© 2015 Wiley Periodicals, Inc.)

The performance of dried blood spots (DBS) polymerase chain reaction (PCR) assays in screening for congenital cytomegalovirus (cCMV) infection varies between different studies. To determine whether the DBS PCR assay has sufficient accuracy to be used as a screening test for cCMV infection, we performed a meta-analysis of 15 studies (n = 26007 neonates) that evaluated the performance of DBS PCR tests in screening for cCMV infection and that met our inclusion criteria. The pooled sensitivity and specificity were 0.844 (95% CI = 0.812-0.872) and 0.999 (95% CI = 0.998-0.999), respectively, and the diagnostic odds ratio was 1362.10 (95%CI = 566.91-3272.60). As sensitivity analysis showed that the results were robust. In conclusion, the performance of DBS PCR assays for testing cCMV was more suitable for retrospective diagnosis than screening.

Background: Interleukin-10 is an important cytokine that regulates immune response. Previous studies have shown that human cytomegalovirus can trigger cell autophagy during the early stages of infection. To our knowledge, whether IL-10 inhibits HCMV-induced autophagy and virus replication has not been studied previously., Objectives: We investigated whether IL-10 affects cell viability and autophagy under the conditions of starvation and HCMV infection by using the MRC5 cell line. We also explored the role of IL-10-mediated autophagy on HCMV replication., Results: Our data showed that IL-10 inhibited the autophagic flux of the MRC5 cells irrespective of starvation or HCMV infection, and suppressed HCMV replication. The promotion of autophagy with either a pharmacological inducer (rapamycin), or a technique to over-express the BECN1 gene reversed the effect of IL-10 on virus replication. Furthermore, the PI3K/Akt signal pathway was activated when the cells were pretreated with IL-10., Conclusions: Our results indicated that IL-10 can suppress HCMV replication by inhibiting autophagy in host cells during the early stages of infection., (Copyright © 2014 Elsevier Inc. All rights reserved.)