Isolation and phylogenetic study of Rift Valley fever virus from the first imported case to China

<正>Dear Editor,Rift Valley fever(RVF)is an anthropozoonosis caused by Rift Valley fever virus(RVFV).RVFV belongs to the Phlebovirus genus in the family Bunyaviridae,which is circulating among ruminants.Human infection with RVFV is generally asymptomatic,however,minority of patients develop severe RVF diseases like encephalitis or     

CD95-CD95L interaction mediates the growth control of MHV68 immortalized B cells by cytotoxic T cells

<正>Dear Editor,The main limitation of the viral pathogenesis study of human gammaherpesviruses Epstein-Barr virus(EBV)and Kaposi sarcoma-associated herpesvirus(KSHV)is the absence of animal model owing to the narrow host tropism of both EBV and KSHV.Murine gammaherpesvirus 68(MHV68)encodes several genes involved in     

Molecular typing of non-polio enteroviruses isolated from acute flaccid paralysis cases in Iran from 2010 to 2015

<正>Dear Editor,Acute flaccid paralysis(AFP)is a complex syndrome often caused by polioviruses.While most countries have eradicated wild polioviruses by vaccination,AFP still remains a health problem in these countries.Most studies have highlighted non-polio enteroviruses(NPEVs)as     

Interplay between hepatitis C virus and ARF4

<正>Dear Editor,Hepatitis C virus(HCV)is a major cause of chronic liver diseases and hepatocellular carcinoma(HCC)with about71 million people globally infected.HCV encodes only10 viral proteins and its replication relies on host proteins.Many host factors including ADP-ribosylation factors     

Hepatitis C virus-induced prion protein expression facilitates hepatitis C virus replication

Hepatitis C virus (HCV) infects approximately 180 million people worldwide. Significant progress has been made since the establishment of in vitro HCV infection models in cells. However, the replication of HCV is complex and not completely understood. Here, we found that the expression of host prion protein (PrP) was induced in an HCV replication cell model. We then showed that increased PrP expression facilitated HCV genomic replication. Finally, we demonstrated that the KKRPK motif on the N-terminus of PrP bound nucleic acids and facilitated HCV genomic replication. Our results provided important insights into how viruses may harness cellular protein to achieve propagation.

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Human cytomegalovirus infection dysregulates neural progenitor cell fate by disrupting Hes1 rhythm and down-regulating its expression

Human cytomegalovirus(HCMV) infection is a leading cause of birth defects, primarily affecting the central nervous system and causing its maldevelopment. As the essential downstream effector of Notch signaling pathway, Hes1, and its dynamic expression, plays an essential role on maintaining neural progenitor/stem cells(NPCs) cell fate and fetal brain development. In the present study, we reported the first observation of Hes1 oscillatory expression in human NPCs, with an approximately1.5 hour periodicity and a Hes1 protein half-life of about 17(17.6 ± 0.2) minutes. HCMV infection disrupts the Hes1 rhythm and down-regulates its expression. Furthermore, we discovered that depleting Hes1 protein disturbed NPCs cell fate by suppressing NPCs proliferation and neurosphere formation, and driving NPCs abnormal differentiation. These results suggested a novel mechanism linking disruption of Hes1 rhythm and down-regulation of Hes1 expression to neurodevelopmental disorders caused by congenital HCMV infection.     

Construction of an infectious cDNA clone of Tembusu virus isolated from breeder Peking ducks

正Dear Editor,Since April 2010,an outbreak of a new disease has elicited symptoms of high fever,loss of appetite,and reduction in egg production in layer ducks in eastern China;this phenomenon has now spread throughout China(Cao et al.,2011;Su et al.,2011).The causative agent of the disease was identified as Tembusu virus(TMUV),which was classified into the genus Flavivirus,     

Characterization of a recombinant Akabane mutant virus with knockout of a nonstructural protein NSs in a pregnant goat model

正Dear Editor,Akabane virus(AKAV),an orthobunyavirus,is transmitted primarily by biting midges and is widely distributed throughout the world except the Europe.AKAV was first isolated from mosquitoes in Japan(Oya et al.,1961).Although pregnant cows,ewes,and goats infected with AKAV exhibit no clinical signs of disease,in utero infections result in abortion,premature birth,stillbirth,and     

Retromer localizes to autophagosomes during HCV replication

<正>Dear Editor,Hepatitis C virus(HCV)is a positive-strand RNA virus that belongs to the genus Hepacivirus within the Flaviviridae family.HCV causes chronic liver diseases,and185 million people are infected(Messina et al.,2015).Currently,there is no approved vaccine to prevent hepatitis C.HCV induces autophagy through elevating reactive oxygen species(ROS)levels via the unfolded     

Lipids,lipid metabolism and Kaposi’s sarcoma-associated herpesvirus pathogenesis

Lipids are essential for mammalian cells to maintain many physiological functions. Emerging evidence has shown that cancer cells can develop specific alterations in lipid biosynthesis and metabolism to facilitate their survival and various malignant behaviors. To date, the precise role of cellular lipids and lipid metabolism in viral oncogenesis is still largely unclear with only a handful of literature covering this topic to implicate lipid metabolism in oncogenic virus associated pathogenesis. In this review, we focus on the role of lipid biosynthesis and metabolism in the pathogenesis of the Kaposi’s sarcoma-associated herpesvirus, a common causative factor for cancers arising in the immunocompromised settings.

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Recombinant canarypox virus expressing the VP2 protein of infectious bursal disease virus induces protection in vaccinated SPF chickens

正Dear Editor,Infectious bursal disease virus(IBDV)causes infectious bursal disease,a highly contagious immunosuppressive disease that affects young chickens and causes economic losses in the poultry industry worldwide.IBDV replicates mainly in actively dividing B lymphocytes within the bursa of Fabricius(BF),leading to immunosuppression in affected flocks(Mahgoub et al.,2012).Viral protein 2(VP2),the only structural component of the IBDV     

Antigenicity of severe fever with thrombocytopenia syndrome virus nucleocapsid protein and its potential application in the virus serodiagnosis

<正>Dear Editor,Severe fever with thrombocytopenia syndrome virus(SFTSV)is a newly identified viral pathogen of the genus Phlebovirus in the family Bunyaviridae(Sun et al.,2012).SFTSV was first identified from patient serum samples in China(Li et al.,2013;Ning et al.,2015).SFTSV can cause a severe hemorrhagic fever-like disease with a reported case fatality rate ranging from 2.5%     

Extracellular vesicles: novel vehicles in herpesvirus infection

Herpesviruses are remarkable pathogens that have evolved multiple mechanisms to evade host immunity, ensuring their proliferation and egress. Among these mechanisms, herpesviruses utilize elaborate extracellular vesicles, including exosomes, for the intricate interplay between infected host and recipient cells. Herpesviruses incorporate genome expression products and direct cellular products into exosomal cargoes. These components alter the content and function of exosomes released from donor cells, thus affecting the downstream signalings of recipient cells. In this way, herpesviruses hijack exosomal pathways to ensure their survival and persistence, and exosomes are emerging as critical mediators for virus infection-associated intercellular communication and microenvironment alteration. In this review, the function and effects of exosomes in herpesvirus infection will be discussed, so that we will have a better understanding about the pathogenesis of herpesviruses.

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Recent advances in synthetic carbohydrate-based human immunodeficiency virus vaccines

An effective vaccine for human immunodeficiency virus (HIV) is urgently needed to prevent HIV infection and progression to acquired immune deficiency syndrome (AIDS). As glycosylation of viral proteins becomes better understood, carbohydrate-based antiviral vaccines against special viruses have attracted much attention. Significant efforts in carbohydrate synthesis and immunogenicity research have resulted in the development of multiple carbohydrate-based HIV vaccines. This review summarizes recent advances in synthetic carbohydrate-based vaccines design strategies and the applications of these vaccines in the prevention of HIV.

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DC-SIGN promotes Japanese encephalitis virus transmission from dendritic cells to T cells via virological synapses

Skin-resident dendritic cells (DCs) likely encounter incoming viruses in the first place, and their migration to lymph nodes following virus capture may promote viral replication. However, the molecular mechanisms underlying these processes remain unclear. In the present study, we found that compared to cell-free viruses, DC-bound viruses showed enhanced capture of JEV by T cells. Additionally, JEV infection was increased by co-culturing DCs and T cells. Blocking the C-type lectin receptor DC-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) with neutralizing antibodies or antagonists blocked JEV transmission to T cells. Live-cell imaging revealed that DCs captured and transferred JEV viral particles to T cells via virological synapses formed at DC-T cell junctions. These findings indicate that DC-SIGN plays an important role in JEV transmission from DCs to T cells and provide insight into how JEV exploits the migratory and antigen-presenting capabilities of DCs to gain access to lymph nodes for dissemination and persistence in the host.

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Productive HBV infection of well-differentiated,hNTCP-expressing human hepatoma-derived (Huh7) cells

Feasible and effective cell models for hepatitis B virus (HBV) infection are required for investigating the complete lifecycle of this virus, including the early steps of viral entry. Resistance to dimethyl sulfoxide/polyethylene glycol (DMSO/PEG), hNTCP expression, and a differentiated state are the limiting factors for successful HBV infection models. In the present study, we used a hepatoma cell line (Huh7D^hNTCP) to overcome these limiting factors so that it exhibits excellent susceptibility to HBV infection. To achieve this goal, different hepatoma cell lines were tested with 2.5% DMSO / 4% PEG8000, and one resistant cell line (Huh7D) was used to construct a stable hNTCP-expressing cell line (Huh7D^hNTCP) using a recombinant lentivirus system. Then, the morphological characteristics and differentiation molecular markers of Huh7D^hNTCP cells with or without DMSO treatment were characterized. Finally, the susceptibility of Huh7D^hNTCP cells to HBV infection was assessed. Our results showed that Huh7D cells were resistant to 2.5% DMSO / 4% PEG8000, whereas the others were not. Huh7D^hNTCP cells were established to express a high level of hNTCP compared to liver extracts, and Huh7D^hNTCP cells rapidly transformed into a non-dividing, well-differentiated polarized phenotype under DMSO treatment. Huh7D^hNTCP cells fully supported the entire lifecycle of HBV infection. This cell culture system will be useful for the analysis of host-virus interactions, which should facilitate the discovery of antiviral drugs and vaccines.

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The regulatory role of protein phosphorylation in human gammaherpesvirus associated cancers

Activation of specific sets of protein kinases by intracellular signal molecules has become more and more apparent in the past decade. Phosphorylation, one of key posttranslational modification events, is activated by kinase or regulatory protein and is vital for controlling many physiological functions of eukaryotic cells such as cell proliferation, differentiation, malignant transformation, and signal transduction mediated by external stimuli. Moreovers, the reversible modification of phosphorylation and dephosphorylation can result in different features of the target substrate molecules including DNA binding, protein-protein interaction, subcellular location and enzymatic activity, and is often hijacked by viral infection. Epstein-Barr virus (EBV) and Kaposi’s sarcomaassociated herpesvirus (KSHV), two human oncogenic gamma-herpesviruses, are shown to tightly associate with many malignancies. In this review, we summarize the recent progresses on understanding of molecular properties and regulatory modes of cellular and viral proteins phosphorylation influenced by these two tumor viruses, and highlight the potential therapeutic targets and strategies against their related cancers.

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Elevated expression of EBV and TLRs in the brain is associated with Rasmussen’s encephalitis

Rasmussen's encephalitis(RE) is a rare pediatric neurological disorder, the etiology of which remains unclear. It has been speculated that the immunopathogenesis of RE involves damage to neurons, which eventually leads to the occurrence of RE. Viral infection may be a critical factor in triggering RE immunopathogenesis. In this study, we analyzed the expression of Epstein-Barr virus(EBV) antigens as well as of Toll-like receptor 3(TLR3), TLR9, and downstream adapter TIRdomain-containing adapter-inducing interferon-β(TRIF) in the brain tissues of 26 patients with RE and 16 control individuals using immunohistochemistry(IHC). In the RE group, EBV antigens were detected in 53% of individuals at various expression levels. In contrast, there was no detectable EBV antigen expression in control brain tissues. Moreover, we found marked increases in the expression of TLR3, TLR9, and TRIF in the brain tissues of RE patients compared with levels in the control group. Furthermore, among RE cases, EBV expression and high TLR3 expression were associated with more severe brain atrophy. Our results suggest that the elevated expression of EBV and TLRs may be involved in RE occurrence through the activation of downstream molecules.