Recently, interferon-induced transmembrane proteins (IFITMs) have been identified to be key effector molecules in the host type I interferon defense system. The invasion of host cells by a large range of RNA viruses is inhibited by IFITMs during the entry step. However, the roles of IFITMs in DNA virus infections have not been studied in detail. In this study, we report that human cytomegalovirus (HCMV), a large human DNA virus, exploits IFITMs to facilitate the formation of the virion assembly compartment (vAC) during infection of human fibroblasts. We found that IFITMs were expressed constitutively in human embryonic lung fibroblasts (MRC5 cells). HCMV infection inhibited IFITM protein accumulation in the later stages of infection. Overexpression of an IFITM protein in MRC5 cells slightly enhanced HCMV production and knockdown of IFITMs by RNA interference reduced the virus titer by about 100-fold on day 8 postinfection, according to the findings of a virus yield assay at a low multiplicity of infection. Virus gene expression and DNA synthesis were not affected, but the typical round structure of the vAC was not formed after the suppression of IFITMs, thereby resulting in defective virion assembly and the production of less infectious virion particles. Interestingly, the replication of herpes simplex virus, a human herpesvirus that is closely related to HCMV, was not affected by the suppression of IFITMs in MRC5 cells. These results indicate that IFITMs are involved in a specific pathway required for HCMV replication. IMPORTANCEHCMV is known to repurpose the interferon-stimulated genes (ISGs) viperin and tetherin to facilitate its replication. Our results expand the range of ISGs that can be exploited by HCMV for its replication. This is also the first report of a proviral function of IFITMs in DNA virus replication. In addition, whereas previous studies showed that IFITMs modulate virus entry, which is a very early stage in the virus life cycle, we identified a new function of IFITMs during the very late stage of virus replication, i.e., virion assembly. Virus entry and assembly both involve vesicle transport and membrane fusion; thus, a common biochemical activity of IFITMs is likely to be involved. Therefore, our findings may provide a new platform for dissecting the molecular mechanism of action of IFITMs during the blocking or enhancement of virus infection, which are under intense investigation in this field. Human cytomegalovirus (HCMV), a ubiquitous opportunistic pathogen that belongs to the Betaherpesviridae subfamily, is a major cause of morbidity and mortality in immunocompromised individuals (1). HCMV infection induces the expression of type I interferon and a set of interferon (IFN)-stimulated genes (ISGs) early upon infection (2, 3). However, HCMV encodes multiple proteins, including IE1 (4-6), IE2 (7-9), pp65 (10, 11), and TRS1 and IRS1 (12, 13), to antagonize the innate immune responses. Moreover, several IFN-induced host restriction factors are repurposed by HCMV to facilitate its repl...

Summary Echinococcosis is a chronic parasitic infectious disease regulated by T‐cell subsets. CD4+ CD25+ FoxP3 +  regulatory T (Treg) cells and Th17 cells have been described as two distinct subsets and have the opposite effect on inflammation. Th17/Treg balance controls inflammation and may play an important role in the pathogenesis of immune evasion. To assess whether this balance was broken, we detected Th17/Treg functions in different levels including cell frequencies, related cytokines secretion and key transcription factors in patients with cystic echincoccosis and healthy controls. The results demonstrated that patients with cystic echinococcosis revealed significant increase in peripheral Treg number, related cytokines (IL‐10 and TGF‐β1) and transcription factor (Foxp3) levels and moderate decrease in Th17 number, related cytokines (IL‐17 and IL‐23) and transcription factor (RORγt) levels as compared with controls. Results indicated that Th17/Treg functional imbalance exists in patients with chronic cystic echinococcosis, suggesting a potential role for Th17/Treg imbalance in the pathogenesis of immune evasion in echinococcosis.

The histone demethylase LSD1 has been known as a key transcriptional coactivator for DNA viruses such as herpes virus. Inhibition of LSD1 was found to block viral genome transcription and lytic replication of DNA viruses. However, RNA virus genomes do not rely on chromatin structure and histone association, and the role of demethylase activity of LSD1 in RNA virus infections is not anticipated. Here, we identify that, contrary to its role in enhancing DNA virus replication, LSD1 limits RNA virus replication by demethylating and activating IFITM3 which is a host restriction factor for many RNA viruses. We have found that LSD1 is recruited to demethylate IFITM3 at position K88 under IFNα treatment. However, infection by either Vesicular Stomatitis Virus (VSV) or Influenza A Virus (IAV) triggers methylation of IFITM3 by promoting its disassociation from LSD1. Accordingly, inhibition of the enzymatic activity of LSD1 by Trans-2-phenylcyclopropylamine hydrochloride (TCP) increases IFITM3 monomethylation which leads to more severe disease outcomes in IAV-infected mice. In summary, our findings highlight the opposite role of LSD1 in fighting RNA viruses comparing to DNA viruses infection. Our data suggest that the demethylation of IFITM3 by LSD1 is beneficial for the host to fight against RNA virus infection.