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  • 刊频: Continuously updated 2017-
  • NLM标题: J Gen Virol
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  • 机译 蜂皇后病毒感染的模式
    摘要:The well-being of a colony and replenishment of the workers depends on a healthy queen. Diseases in queens are seldom reported, and our knowledge on viral infection in queens is limited. In this study, 86 honey bee queens were collected from beekeepers in Denmark. All queens were tested separately by two real-time PCRs: one for the presence of deformed wing virus (DWV), and one that would detect sequences of acute bee-paralysis virus, Kashmir bee virus and Israeli acute paralysis virus (AKI complex). Worker bees accompanying the queen were also analysed. The queens could be divided into three groups based on the level of infection in their head, thorax, ovary, intestines and spermatheca. Four queens exhibited egg-laying deficiency, but visually all queens appeared healthy. Viral infection was generally at a low level in terms of AKI copy numbers, with 134/430 tissues (31 %) showing the presence of viral infection ranging from 101 to 105 copies. For DWV, 361/340 tissues (84 %) showed presence of viral infection (DWV copies ranging from 102 to 1012), with 50 tissues showing viral titres >107 copies. For both AKI and DWV, the thorax was the most frequently infected tissue and the ovaries were the least frequently infected. Relative to total mass, the spermatheca showed significantly higher DWV titres than the other tissues. The ovaries had the lowest titre of DWV. No significant differences were found among tissues for AKI. A subsample of 14 queens yielded positive results for the presence of negative-sense RNA strands, thus demonstrating active virus replication in all tissues.
  • 机译 爱泼斯坦-巴尔病毒潜伏膜蛋白1对人鼻咽细胞和鼻咽癌中AT特异结合蛋白1的上调
    摘要:A global regulator of chromatin remodelling and gene expression, special AT-rich-binding protein 1 (SATB1) has been implicated in promotion of growth and metastasis of a number of cancers. Here, we demonstrate that the principal oncogene of Epstein–Barr virus (EBV), latent membrane protein 1 (LMP1) upregulates SATB1 RNA and protein expression in human nasopharyngeal cell lines. Silencing of endogenously expressed SATB1 with specific short hairpin RNA decreases cell proliferation and resistance to apoptosis induced by growth factor withdrawal. Additionally, we provide evidence that LMP1-mediated expression of Survivin, a multifunctional protein involved in promoting cell growth and survival, is mediated at least in part by SATB1 in human nasopharyngeal cells. Finally, we show that SATB1 protein levels are elevated in tissue samples from patients with nasopharyngeal carcinoma (NPC), and are directly correlated with the expression of LMP1. Taken together, our results suggest that SATB1 functions as a pro-metastatic effector of LMP1 signalling in EBV-positive NPC.
  • 机译 猕猴猕猴活体减毒猿猴免疫缺陷病毒疫苗接种后TRIM5α基因表达上调但TRIM5α基因型对病毒获取或疫苗接种结果没有影响
    摘要:Polymorphism in the TRIM5α/TRIMcyp gene, which interacts with the lentiviral capsid, has been shown to impact on simian immunodeficiency virus (SIV) replication in certain macaque species. Here, in the context of a live-attenuated SIV vaccine study conducted in Mauritian-origin cynomolgus macaques (MCM), we demonstrate upregulation of TRIM5α expression in multiple lymphoid tissues immediately following vaccination. Despite this, the restricted range of TRIM5α genotypes and lack of TRIMcyp variants had no or only limited impact on the replication kinetics in vivo of either the SIVmac viral vaccine or wild-type SIVsmE660 challenge. Additionally, there appeared to be no impact of TRIM5α genotype on the outcome of homologous or heterologous vaccination/challenge studies. The limited spectrum of TRIM5α polymorphism in MCM appears to minimize host bias to provide consistency of replication for SIVmac/SIVsm viruses in vivo, and therefore on vaccination and pathogenesis studies conducted in this species.
  • 机译 狂犬病街头病毒导致海马体发生树突状损伤和F-肌动蛋白解聚
    摘要:Rabies is an acute viral infection of the central nervous system and is typically fatal in humans and animals; however, its pathogenesis remains poorly understood. In this study, the morphological changes of dendrites and dendritic spines in the CA1 region of the hippocampus were investigated in mice that were infected intracerebrally with an MRV strain of the street rabies virus. Haematoxylin and eosin and fluorescence staining analysis of brain sections from the infected mice showed very few morphological changes in the neuronal bodies and neuronal processes. However, we found a significant decrease in the number of dendritic spines. Primary neuronal cultures derived from the hippocampus of mice (embryonic day 16.5) that were infected with the virus also showed an obvious decrease in the number of dendritic spines. Furthermore, the decrease in the number of dendritic spines was related to the depolymerization of actin filaments (F-actin). We propose that the observed structural changes can partially explain the severe clinical disease that was found in experimental models of street rabies virus infections.
  • 机译 Theiler的鼠类脑脊髓炎病毒与脑心肌炎和口蹄疫病毒形成鲜明对比其功能是利用StopGo非标准翻译机制
    摘要:The picornaviruses’ genome consists of a positive-sense ssRNA. Like many picornaviruses, cardioviruses synthesize two distinct polyprotein precursors from adjacent but non-overlapping genome segments. Both the [L-1ABCD-2A] and the [2BC-3ABCD] polyproteins are proteolytically processed to yield mature capsid and non-structural proteins, respectively. An unusual translational event, known as ‘StopGo’ or ‘Stop-Carry on’, is responsible for the release of the [L-1ABCD-2A] polyprotein from the ribosome and synthesis of the N-terminal amino acid of the [2BC-3ABCD] polyprotein. A common feature of these viruses is the presence of a highly conserved signature sequence for StopGo: –D(V/I)ExNPGP–, where –D(V/I)ExNPG are the last 7 aa of 2A, and the last P- is the first amino acid of 2B. Here, we report that, in contrast to encephalomyocarditis virus and foot-and-mouth disease virus, a functional StopGo does not appear to be essential for Theiler’s murine encephalomyelitis virus viability when tested in vitro and in vivo.
  • 机译 西尼罗河病毒NS2A蛋白独立于干扰素应答而促进病毒诱导的凋亡
    摘要:The flavivirus NS2A protein is a small, multifunctional protein, involved in replication, virion formation and regulation of the innate immune response. Using the Kunjin strain of West Nile virus (WNVKUN) we previously demonstrated that a single amino acid change from alanine to proline at position 30 of the NS2A protein (A30P) reduced viral cytopathicity in cells and virulence in mice. To further investigate functions of the NS2A protein we have substituted alanine at position 30 with different amino acids (A30 mutants) in a WNVKUN infectious clone. The virulence of mutant viruses in wild-type (WT) and IRF3/IRF7 double-knockout mice was influenced by the amino acid change and ranged from high to low in the order of WT>A30L>A30E>A30P/A30G. Moreover, infection of beta interferon (IFN-β)-deficient Vero cells with A30P virus showed less pronounced chromosomal DNA degradation and lower percentage of cells with positive TUNEL labelling than in WT virus infection, indicating a role for the WT NS2A protein in IFN-independent apoptotic cell death.
  • 机译 p53通过NF-κB和PI3K–Akt途径控制丙型肝炎病毒非结构蛋白5A介导的GADD45α表达下调
    摘要:Growth arrest and DNA-damage-inducible gene 45-α (GADD45α) protein has been shown to be a tumour suppressor and is implicated in cell-cycle arrest and suppression of cell growth. The hepatitis C virus (HCV) non-structural 5A (NS5A) protein plays an important role in cell survival and is linked to the development of hepatocellular carcinoma (HCC). However, the role of HCV NS5A in the development of HCC remains to be clarified. This study sought to determine whether GADD45α mediates HCV NS5A-induced cellular survival and to elucidate the molecular mechanism of GADD45α expression regulated by HCV NS5A. It was found that HCV NS5A downregulated GADD45α expression at the transcriptional level by decreasing promoter activity, mRNA transcription and protein levels. Knockdown of p53 resulted in a similar decrease in GADD45α expression to that caused by HCV NS5A, whilst overexpression of p53 reversed the HCV NS5A-mediated downregulation of GADD45α. HCV NS5A repressed p53 expression, which was followed by a subsequent decrease in GADD45α expression. Further evidence was provided showing that HCV NS5A led to increases of phosphorylated nuclear factor-κB and Akt levels. Inhibition of these pathways using pharmacological inhibitors or specific small interfering RNAs rescued HCV NS5A-mediated downregulation of p53 and GADD45α. It was also found that HCV NS5A protein and depletion of GADD45α increased cell growth, whereas ectopic expression of GADD45α eliminated HCV NS5A-induced cell proliferation. These results indicated that HCV NS5A downregulates GADD45α expression and subsequently triggers cellular proliferation. These findings provide new insights suggesting that HCV NS5A could contribute to the occurrence of HCV-related HCC.
  • 机译 Toll样受体7抑制神经元中的病毒复制但不影响兰加特病毒感染的小鼠模型中的病毒发病机理
    摘要:Toll-like receptor 7 (TLR7) recognizes guanidine-rich viral ssRNA and is an important mediator of peripheral immune responses to several ssRNA viruses. However, the role that TLR7 plays in regulating the innate immune response to ssRNA virus infections in specific organs such as the central nervous system (CNS) is not as clear. This study examined the influence of TLR7 on the neurovirulence of Langat virus (LGTV), a ssRNA tick-borne flavivirus. TLR7 deficiency did not substantially alter the onset or incidence of LGTV-induced clinical disease; however, it did significantly affect virus levels in the CNS with a log10 increase in virus titres in brain tissue from TLR7-deficient mice. This difference in virus load was also observed following intracranial inoculation, indicating a direct effect of TLR7 deficiency on regulating virus replication in the brain. LGTV-induced type I interferon responses in the CNS were not dependent on TLR7, being higher in TLR7-deficient mice compared with wild-type controls. In contrast, induction of pro-inflammatory cytokines including tumour necrosis factor, CCL3, CCL4 and CXCL13 were dependent on TLR7. Thus, although TLR7 is not essential in controlling LGTV pathogenesis, it is important in controlling virus infection in neurons in the CNS, possibly by regulating neuroinflammatory responses.
  • 机译 人cathelicidin LL-37通过不同于表面活性剂蛋白D或防御素的机制抑制甲型流感病毒
    摘要:LL-37, the only human cathelicidin, is a cationic antimicrobial peptide with antibacterial and antifungal activity. LL-37 is released from neutrophil granules and produced by epithelial cells. It has been implicated in host defence against influenza A virus (IAV) in recent studies. We now demonstrate dose-related neutralizing activity of LL-37 against several seasonal and mouse-adapted IAV strains. The ability of LL-37 to inhibit these IAV strains resulted mainly from direct effects on the virus, since pre-incubation of virus with LL-37 was needed for optimal inhibition. LL-37 bound high-density lipoprotein (HDL), and pre-incubation of LL-37 with human serum or HDL reduced its antiviral activity. LL-37 did not inhibit viral association with epithelial cells as assessed by quantitative RT-PCR or confocal microscopy. This finding contrasted with results obtained with surfactant protein D (SP-D). Unlike collectins or human neutrophil defensins (HNPs), LL-37 did not induce viral aggregation under electron microscopy. In the electron microscopy studies, LL-37 appeared to cause disruption of viral membranes. LL-37 had additive antiviral activity when combined with other innate inhibitors like SP-D, surfactant protein A and HNPs. Unlike HNPs, LL-37 did not bind SP-D significantly. These findings indicate that LL-37 contributes to host defence against IAV through a mechanism distinct from that of SP-D and HNPs.
  • 机译 ISG56 / IFIT1主要负责干扰素诱导的副流感病毒5型转录和蛋白质合成模式的变化
    摘要:Interferon (IFN) induces an antiviral state in cells that results in alterations of the patterns and levels of parainfluenza virus type 5 (PIV5) transcripts and proteins. This study reports that IFN-stimulated gene 56/IFN-induced protein with tetratricopeptide repeats 1 (ISG56/IFIT1) is primarily responsible for these effects of IFN. It was shown that treating cells with IFN after infection resulted in an increase in virus transcription but an overall decrease in virus protein synthesis. As there was no obvious decrease in the overall levels of cellular protein synthesis in infected cells treated with IFN, these results suggested that ISG56/IFIT1 selectively inhibits the translation of viral mRNAs. This conclusion was supported by in vitro translation studies. Previous work has shown that ISG56/IFIT1 can restrict the replication of viruses lacking a 2′-O-methyltransferase activity, an enzyme that methylates the 2′-hydroxyl group of ribose sugars in the 5′-cap structures of mRNA. However, the data in the current study strongly suggested that PIV5 mRNAs are methylated at the 2′-hydroxyl group and thus that ISG56/IFIT1 selectively inhibits the translation of PIV5 mRNA by some as yet unrecognized mechanism. It was also shown that ISG56/IFIT1 is primarily responsible for the IFN-induced inhibition of PIV5.
  • 机译 在秘鲁的呼吸道样本中发现的两种新型人类肠道病毒C基因型的基因组分析
    摘要:We report the discovery of two enteroviruses detected in nasopharyngeal samples obtained from subjects with respiratory disease in Peru. Phylogenetic analysis indicated that both viruses belong to a clade within the species Human enterovirus C, which includes the recently characterized human enteroviruses 109 and 104. Members of this clade have undergone significant genomic rearrangement, as indicated by deletions in the hypervariable region of the 5′ UTR and the VP1 protein, as well as recombination within the non-structural genes. Our findings and review of published sequences suggests that several novel human enterovirus C serotypes are currently circulating worldwide.
  • 机译 dsRNA腺苷脱氨酶ADAR-1对2型人T细胞白血病病毒和3型猿猴T细胞白血病病毒的超编辑
    摘要:RNA editing mediated by adenosine deaminases acting on RNA (ADARs) converts adenosine (A) to inosine (I) residues in dsRNA templates. While ADAR-1-mediated editing was essentially described for RNA viruses, the present work addresses the issue for two δ-retroviruses, human T-cell leukemia virus type 2 and simian T-cell leukemia virus type 3 (HTLV-2 and STLV-3). We examined whether ADAR-1 could edit HTLV-2 and STLV-3 virus genomes in cell culture and in vivo. Using a highly sensitive PCR-based method, referred to as 3DI-PCR, we showed that ADAR-1 could hypermutate adenosine residues in HTLV-2. STLV-3 hypermutation was obtained without using 3DI-PCR, suggesting a higher mutation frequency for this virus. Detailed analysis of the dinucleotide editing context showed preferences for 5′ ArA and 5′ UrA. In conclusion, the present observations demonstrate that ADAR-1 massively edits HTLV-2 and STLV-3 retroviruses in vitro, but probably remains a rare phenomenon in vivo.
  • 机译 1998-2011年北美猪中甲型流感病毒的基因组重排
    摘要:Revealing the frequency and determinants of reassortment among RNA genome segments is fundamental to understanding basic aspects of the biology and evolution of the influenza virus. To estimate the extent of genomic reassortment in influenza viruses circulating in North American swine, we performed a phylogenetic analysis of 139 whole-genome viral sequences sampled during 1998–2011 and representing seven antigenically distinct viral lineages. The highest amounts of reassortment were detected between the H3 and the internal gene segments (PB2, PB1, PA, NP, M and NS), while the lowest reassortment frequencies were observed among the H1γ, H1pdm and neuraminidase segments, particularly N1. Less reassortment was observed among specific haemagglutinin–neuraminidase combinations that were more prevalent in swine, suggesting that some genome constellations may be evolutionarily more stable.
  • 机译 水泡性口腔炎病毒作为溶瘤病毒疗法抗癌的灵活平台
    摘要:Oncolytic virus (OV) therapy is an emerging anti-cancer approach that utilizes viruses to preferentially infect and kill cancer cells, while not harming healthy cells. Vesicular stomatitis virus (VSV) is a prototypic non-segmented, negative-strand RNA virus with inherent OV qualities. Antiviral responses induced by type I interferon pathways are believed to be impaired in most cancer cells, making them more susceptible to VSV than normal cells. Several other factors make VSV a promising OV candidate for clinical use, including its well-studied biology, a small, easily manipulated genome, relative independence of a receptor or cell cycle, cytoplasmic replication without risk of host-cell transformation, and lack of pre-existing immunity in humans. Moreover, various VSV-based recombinant viruses have been engineered via reverse genetics to improve oncoselectivity, safety, oncotoxicity and stimulation of tumour-specific immunity. Alternative delivery methods are also being studied to minimize premature immune clearance of VSV. OV treatment as a monotherapy is being explored, although many studies have employed VSV in combination with radiotherapy, chemotherapy or other OVs. Preclinical studies with various cancers have demonstrated that VSV is a promising OV; as a result, a human clinical trial using VSV is currently in progress.
  • 机译 病毒线粒体局部凋亡抑制剂(UL37外显子1蛋白)不能保护人类神经前体细胞免受人类巨细胞病毒诱导的细胞死亡
    摘要:Congenital human cytomegalovirus (HCMV) infection can cause severe brain abnormalities. Apoptotic HCMV-infected brain cells have been detected in a congenitally infected infant. In biologically relevant human neural precursor cells (hNPCs), cultured in physiological oxygen tensions, HCMV infection (m.o.i. of 1 or 3) induced cell death within 3 days post-infection (p.i.) and increased thereafter. Surprisingly, its known anti-apoptotic genes, including the potent UL37 exon 1 protein (pUL37x1) or viral mitochondria-localized inhibitor of apoptosis (vMIA), which protects infected human fibroblasts (HFFs) from apoptosis and from caspase-independent, mitochondrial serine protease-mediated cell death, were expressed by 2 days p.i. Consistent with this finding, an HCMV UL37x1 mutant, BADsubstitutionUL37x1 (BADsubUL37x1) induced cell death in hNPCs (m.o.i. = 1) to level which were indistinguishable from parental virus (BADwild-type)-infected hNPCs. Surprisingly, although BADsubUL37x1 is growth defective in permissive HFFs, it produced infectious progeny in hNPCs with similar kinetics and to levels comparable to BADwild-type-infected hNPCs (m.o.i. = 1). While delayed at a lower multiplicity (m.o.i. = 0.3), the BADsubUL37x1 mutant reached similar levels to revertant within 12 days, in contrast to its phenotype in HFFs. The inability of pUL37x1/vMIA to protect hNPCs from HCMV-induced cell death did not result from impaired trafficking as pUL37x1/vMIA trafficked efficiently to mitochondria in transfected hNPCs and in HCMV-infected hNPCs. These results establish that pUL37x1/vMIA, although protective in permissive HFFs, does not protect HCMV-infected hNPCs from cell death under physiologically relevant oxygen tensions. They further suggest that pUL37x1/vMIA is not essential for HCMV growth in hNPCs and has different cell type-specific roles.
  • 机译 对16种科罗拉多州人类NL63冠状病毒的基因组分析确定了一种新基因型穗基因N末端结构域的高序列多样性以及重组的证据
    摘要:This study compared the complete genome sequences of 16 NL63 strain human coronaviruses (hCoVs) from respiratory specimens of paediatric patients with respiratory disease in Colorado, USA, and characterized the epidemiology and clinical characteristics associated with circulating NL63 viruses over a 3-year period. From 1 January 2009 to 31 December 2011, 92 of 9380 respiratory specimens were found to be positive for NL63 RNA by PCR, an overall prevalence of 1 %. NL63 viruses were circulating during all 3 years, but there was considerable yearly variation in prevalence and the month of peak incidence. Phylogenetic analysis comparing the genome sequences of the 16 Colorado NL63 viruses with those of the prototypical hCoV-NL63 and three other NL63 viruses from the Netherlands demonstrated that there were three genotypes (A, B and C) circulating in Colorado from 2005 to 2010, and evidence of recombination between virus strains was found. Genotypes B and C co-circulated in Colorado in 2005, 2009 and 2010, but genotype A circulated only in 2005 when it was the predominant NL63 strain. Genotype C represents a new lineage that has not been described previously. The greatest variability in the NL63 virus genomes was found in the N-terminal domain (NTD) of the spike gene (nt 1–600, aa 1–200). Ten different amino acid sequences were found in the NTD of the spike protein among these NL63 strains and the 75 partial published sequences of NTDs from strains found at different times throughout the world.
  • 机译 大流行H1N1病毒基因重配的H9流感病毒的致病性和传播性
    摘要:Both H9N2 avian influenza and 2009 pandemic H1N1 viruses (pH1N1) are able to infect humans and swine, which has raised concerns that novel reassortant H9 viruses with pH1N1 genes might be generated in these hosts by reassortment. Although previous studies have demonstrated that reassortant H9 viruses with pH1N1 genes show increased virulence in mice and transmissibility in ferrets, the virulence and transmissibility of reassortant H9 viruses in natural hosts such as chickens and swine remain unknown. This study generated two reassortant H9 viruses (H9N2/CA09 and H9N1/CA09) in the background of the pH1N1 A/California/04/2009 (CA09) virus by replacing either both the haemagglutinin (HA) and neuraminidase (NA) genes or only the HA gene with the respective genes from the A/quail/Hong Kong/G1/1997 (H9N2) virus and evaluated their replication, pathogenicity and transmission in chickens and pigs compared with the parental viruses. Chickens that were infected with the parental H9N2 and reassortant H9 viruses seroconverted. The parental H9N2 and reassortant H9N2/CA09 viruses were transmitted to sentinel chickens, but H9N1/CA09 virus was not. The parental H9N2 replicated poorly and was not transmitted in pigs, whereas both H9N2/CA09 and H9N1/CA09 viruses replicated and were transmitted efficiently in pigs, similar to the pH1N1 virus. These results demonstrated that reassortant H9 viruses with pH1N1 genes show enhanced replication and transmissibility in pigs compared with the parental H9N2 virus, indicating that they may pose a threat for humans if such reassortants arise in swine.
  • 机译 估计共同传播的欧亚猪流感病毒的重配率
    摘要:Swine have often been considered as a mixing vessel for different influenza strains. In order to assess their role in more detail, we undertook a retrospective sequencing study to detect and characterize the reassortants present in European swine and to estimate the rate of reassortment between H1N1, H1N2 and H3N2 subtypes with Eurasian (avian-like) internal protein-coding segments. We analysed 69 newly obtained whole genome sequences of subtypes H1N1–H3N2 from swine influenza viruses sampled between 1982 and 2008, using Illumina and 454 platforms. Analyses of these genomes, together with previously published genomes, revealed a large monophyletic clade of Eurasian swine-lineage polymerase segments containing H1N1, H1N2 and H3N2 subtypes. We subsequently examined reassortments between the haemagglutinin and neuraminidase segments and estimated the reassortment rates between lineages using a recently developed evolutionary analysis method. High rates of reassortment between H1N2 and H1N1 Eurasian swine lineages were detected in European strains, with an average of one reassortment every 2–3 years. This rapid reassortment results from co-circulating lineages in swine, and in consequence we should expect further reassortments between currently circulating swine strains and the recent swine-origin H1N1v pandemic strain.
  • 机译 表位标记的口蹄疫病毒的特征
    摘要:Foot-and-mouth disease (FMD) is a highly contagious and economically devastating disease of cloven-hoofed animals with an almost-worldwide distribution. Conventional FMD vaccines consisting of chemically inactivated viruses have aided in the eradication of FMD from Europe and remain the main tool for control in endemic countries. Although significant steps have been made to improve the quality of vaccines, such as improved methods of antigen concentration and purification, manufacturing processes are technically demanding and expensive. Consequently, there is large variation in the quality of vaccines distributed in FMD-endemic countries compared with those manufactured for emergency use in FMD-free countries. Here, we have used reverse genetics to introduce haemagglutinin (HA) and FLAG tags into the foot-and-mouth disease virus (FMDV) capsid. HA- and FLAG-tagged FMDVs were infectious, with a plaque morphology similar to the non-tagged parental infectious copy virus and the field virus. The tagged viruses utilized integrin-mediated cell entry and retained the tag epitopes over serial passages. In addition, infectious HA- and FLAG-tagged FMDVs were readily purified from small-scale cultures using commercial antibodies. Tagged FMDV offers a feasible alternative to the current methods of vaccine concentration and purification, a potential to develop FMD vaccine conjugates and a unique tool for FMDV research.
  • 机译 呼吸道合胞病毒修饰调控影响病毒复制的宿主基因的微RNA
    摘要:Respiratory syncytial virus (RSV) causes substantial morbidity and life-threatening lower respiratory tract disease in infants, young children and the elderly. Understanding the host response to RSV infection is critical for developing disease-intervention approaches. The role of microRNAs (miRNAs) in post-transcriptional regulation of host genes responding to RSV infection is not well understood. In this study, it was shown that RSV infection of a human alveolar epithelial cell line (A549) induced five miRNAs (let-7f, miR-24, miR-337-3p, miR-26b and miR-520a-5p) and repressed two miRNAs (miR-198 and miR-595), and showed that RSV G protein triggered let-7f expression. Luciferase–untranslated region reporters and miRNA mimics and inhibitors validated the predicted targets, which included cell-cycle genes (CCND1, DYRK2 and ELF4), a chemokine gene (CCL7) and the suppressor of cytokine signalling 3 gene (SOCS3). Modulating let-7 family miRNA levels with miRNA mimics and inhibitors affected RSV replication, indicating that RSV modulates host miRNA expression to affect the outcome of the antiviral host response, and this was mediated in part through RSV G protein expression.

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