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(1) High Constitutive IL-10 Interferes with the Immune Response to Varicella-Zoster Virus (VZV) in Elderly Recipients of Live Attenuated Zoster Vaccine.[TOP]

Pubmed ID :30445431
Publication Date : //
Live attenuated zoster vaccine (Zostavax™) was used to test the hypothesis that constitutive IL-10, which may be high in elderly subjects, impairs vaccine efficacy. If true, then effectiveness of viral vaccines might be improved by transient inhibition of IL-10 before vaccination.

Authors : Gershon Anne A, Brooks David, Stevenson Donald D, Chin William K, Oldstone Michael B A, Gershon Michael D,

(2) Herpesvirus and Autophagy: "All Right, Everybody Be Cool, This Is a Robbery!"[TOP]

Pubmed ID :29207540
Publication Date : //
Autophagy is an essential vacuolar process of the cell, leading to lysosomal degradation and recycling of proteins and organelles, which is extremely important in maintaining homeostasis. Multiple roles have been now associated with autophagy, in particular a pro-survival role in nutrient starvation or in stressful environments, a role in life span extension, in development, or in innate and adaptive immunity. This cellular process can also take over microorganisms or viral proteins inside autophagosomes and degrade them directly in autolysosomes and is then called xenophagy and virophagy, respectively. Several Herpesviruses have developed strategies to escape this degradation, by expression of specific anti-autophagic proteins. However, we are increasingly discovering that Herpesviruses hijack autophagy, rather than just fight it. This beneficial effect is obvious since inhibition of autophagy will lead to decreased viral titers for human cytomegalovirus (HCMV), Epstein-Barr virus (EBV) or Varicella-Zoster virus (VZV), for example. Conversely, autophagy stimulation will improve viral multiplication. The autophagic machinery can be used in whole or in part, and can optimize viral propagation or persistence. Some viruses block maturation of autophagosomes to avoid the degradation step, then autophagosomal membranes are used to contribute to the envelopment and/or the egress of viral particles. On the other hand, VZV stimulates the whole process of autophagy to subvert it in order to use vesicles containing ATG (autophagy-related) proteins and resembling amphisomes for their transport in the cytoplasm. During latency, autophagy can also be activated by latent proteins encoded by different oncogenic Herpesviruses to promote cell survival and achieve long term viral persistence in vivo. Finally, reactivation of gammaherpesvirus Murid Herpesvirus 68 (MHV68) in mice appears to be positively modulated by autophagy, in order to control the level of inflammation. Therefore, Herpesviruses appear to behave more like thieves than fugitives.

Authors : Lussignol Marion, Esclatine Audrey,

(3) Schlafen 14 (SLFN14) is a novel antiviral factor involved in the control of viral replication.[TOP]

Pubmed ID :28734654
Publication Date : //
Schlafen (SLFN) proteins have been suggested to play important functions in cell proliferation and immune cell development. In this study, we determined the antiviral activities of putative RNA-helicase domain-containing SLFN14. Murine SLFN14 expression was specifically induced by TLR3-mediated pathways and type I interferon (IFN) in RAW264.7 mouse macrophages. To examine the role of SLFN during viral infection, cells were infected with either wild-type PR8 or delNS1/PR8 virus. SLFN14 expression was specifically induced following influenza virus infection. Overexpression of SLFN14 in A549 cells reduced viral replication, whereas knockdown of SLFN14 in RAW264.7 cells enhanced viral titers. Furthermore, SLFN14 promoted the delay in viral NP translocation from cytoplasm to nucleus and enhanced RIG-I-mediated IFN-β signaling. In addition, SLFN14 overexpression promoted antiviral activity against varicella zoster virus (VZV), a DNA virus. In conclusion, our data suggest that SLFN14 is a novel antiviral factor for both DNA and RNA viruses.

Authors : Seong Rak-Kyun, Seo Seong-Wook, Kim Ji-Ae, Fletcher Sarah J, Morgan Neil V, Kumar Mukesh, Choi Young-Ki, Shin Ok Sarah,

(4) Anti-herpes simplex virus type 1 activity of Houttuynoid A, a flavonoid from Houttuynia cordata Thunb.[TOP]

Pubmed ID :28629987
Publication Date : //
Early events in herpes simplex virus type 1 (HSV-1) infection reactivate latent human immunodeficiency virus, Epstein-Barr virus, and human papillomavirus in the presence of acyclovir (ACV). The common use of nucleoside analog medications, such as ACV and pencyclovir, has resulted in the emergence of drug-resistant HSV-1 strains in clinical therapy. Therefore, new antiherpetics that can inhibit early events in HSV-1 infection should be developed. An example of this treatment is Houttuynia cordata Thunb. water extract, which can inhibit HSV-1 infection through multiple mechanisms. In this study, the anti-HSV-1 activity of Houttuynoid A, a new type of flavonoid isolated from H. cordata, was investigated. Three different assays confirmed that this compound could exhibit strong in vitro anti-HSV-1 activity. One assay verified that this compound could inhibit HSV-1 multiplication and prevent lesion formation in a HSV-1 infection mouse model. Mechanism analysis revealed that this compound could inactivate HSV-1 infectivity by blocking viral membrane fusion. Moreover, Houttuynoid A exhibited antiviral activities against other alpha herpes viruses, such as HSV-2 and varicella zoster virus (VZV). In conclusion, Houttuynoid A may be a useful antiviral agent for HSV-1.

Authors : Li Ting, Liu Libao, Wu Hongling, Chen Shaodan, Zhu Qinchang, Gao Hao, Yu Xiongtao, Wang Yi, Su Wenhan, Yao Xinsheng, Peng Tao,

(5) Ethnopharmacological uses, phytochemistry, biological activities, and therapeutic applications of Clinacanthus nutans (Burm. f.) Lindau: A comprehensive review.[TOP]

Pubmed ID :28495603
Publication Date : //
Clinacanthus nutans (Burm. f.) Lindau, a widely used medicinal plant, is extensively grown in tropical Asia and Southeast Asian countries. C. nutans, with its broad spectrum of pharmacological activities, has been traditionally used to treat cancer, inflammatory disorders, diabetes, insect bites, and skin problems, consumed as a vegetable, mixed with fresh juices, in concoctions, and as a whole plant. The present review analyzes the advances in the ethnopharmacology, phytochemistry, pharmacology, and toxicology of C. nutans. In addition, the needs and perspectives for future investigation of this plant are addressed.

Authors : Kamarudin Muhamad Noor Alfarizal, Sarker Md Moklesur Rahman, Kadir Habsah Abdul, Ming Long Chiau,

(6) A novel combined vaccine based on monochimeric VLP co-displaying multiple conserved epitopes against enterovirus 71 and varicella-zoster virus.[TOP]

Pubmed ID :28408118
Publication Date : //
Chicken pox and hand, foot and mouth disease (HFMD) are two major infectious diseases that mainly affect infants and children, causing significant morbidity annually. Varicella-zoster virus (VZV) and enterovirus 71 (EV71), respectively, are the principal epidemic pathogens causing these two diseases. To investigate the possibility of developing a novel combined vaccine to prevent chicken pox and HFMD, we constructed three chimeric virus-like particles (VLPs) (termed HBc-V/1/2, HBc-2/V/1 and HBc-1/2/V) based on the hepatitis B core antigen (HBc) carrier that display epitopes derived from VZV-gE, EV71-VP1, and EV71-VP2 in a varied tandem manner. The chimeric HBc can self-assemble into VLPs with these three epitopes displayed on the surface of particles. Epitope-specific antibody characterization suggested that HBc-V/1/2 elicits a balanced antibody response toward these three epitopes, and no immune interference was observed between the three epitopes. Importantly, the anti-HBc-V/1/2 sera could simultaneously neutralize VZV and EV71 and cross-neutralize coxsackievirus A16 (CVA16), another major pathogen causing HFMD. Moreover, the anti-HBc-V/1/2 sera protected neonatal mice from lethal challenge of EV71 and CVA16. Collectively, our study not only demonstrated that HBc-V/1/2 is a promising candidate combined vaccine for HFMD and Chicken pox but also provides a novel strategy for the design of combined vaccines.

Authors : Wu Yangtao, Zhu Rui, Xu Longfa, Li Yongchao, Li Shuxuan, Yu Hai, Li Shaowei, Zhu Hua, Cheng Tong, Xia Ningshao,

(7) No detection of varicella-zoster virus in temporal arteries of patients with giant cell arteritis.[TOP]

Pubmed ID :28274481
Publication Date : //
Data on the presence of varicella-zoster virus (VZV) in temporal arteries of patients with giant cell arteritis (GCA) are controversial. We analyzed VZV infection in temporal arteries from Italian patients with temporal artery biopsy (TAB)-positive GCA, TAB-negative GCA, and controls.

Authors : Muratore Francesco, Croci Stefania, Tamagnini Ione, Zerbini Alessandro, Bellafiore Salvatore, Belloni Lucia, Boiardi Luigi, Bisagni Alessandra, Pipitone Nicolò, Parmeggiani Maria, Cavazza Alberto, Salvarani Carlo,

(8) Characterization of a thienylcarboxamide derivative that inhibits the transactivation functions of cytomegalovirus IE2 and varicella zoster virus IE62.[TOP]

Pubmed ID :28161581
Publication Date : //
Previously we established reporter cell lines for human cytomegalovirus (HCMV) and varicella zoster virus (VZV) and identified several antiviral compounds against these viruses using the reporter cells. In this study, we found that one of the identified anti-HCMV compounds, a thienylcarboxamide derivative (coded as 133G4), was effective against not only HCMV but also VZV. The following findings indicate that 133G4 inhibits the activation of early gene promoters by HCMV IE2 and VZV IE62: i) 133G4 decreased the expression of HCMV early and late genes but not that of HCMV IE1/IE2 in HCMV-infected cells, ii) 133G4 inhibited the activation of several HCMV early gene promoters of transiently-transfected plasmids in HCMV-infected cells, and iii) in transient transfection assays, 133G4 decreased the activation of HCMV (or VZV) early gene promoters by HCMV IE2 (or VZV IE62) in the absence of other viral protein expression. The inhibition of early gene activation was observed in the human and African green monkey cell lines but not in the rodent cell lines, and the compound was not effective against murine CMV. In addition, VZV IE62 activated HCMV early promoters, and 133G4 still inhibited such promoter activation. Therefore, we hypothesized that 133G4 targets a cellular factor used commonly in activation of human herpesvirus promoters and examined whether 133G4 affects the functions of cellular proteins USF1, TBP, Med25 and EAP, the involvement of which in VZV IE62-dependent viral gene activation has been well characterized. Our experimental results using one-hybrid and bimolecular fluorescence complementation assays demonstrated that 133G4 did not inhibit the recruitment of USF1 or TBP to their binding sites, nor inhibited the direct interactions of VZV IE62 with Med25 and EAP. Thus, 133G4 is a unique anti-VZV and -HCMV compound, which warrants further studies to find out its inhibitory mechanism.

Authors : Majima Ryuichi, Shindoh Keiko, Yamaguchi Toyofumi, Inoue Naoki,

(9) Synthesis, anti-varicella-zoster virus and anti-cytomegalovirus activity of quinazoline-2,4-diones containing isoxazolidine and phosphonate substructures.[TOP]

Pubmed ID :27750154
Publication Date : //
Cycloadditions of N-substituted C-(diethoxyphosphoryl)nitrones to N-allylated quinazoline-2,4-diones functionalized at N3 with substituted benzoyl or benzyl groups proceeded with moderate to good diastereoselectivities (d.e. 28-68%). The synthesized isoxazolidine phosphonates were assessed for the antiviral activity against a broad range of DNA and RNA viruses. Compounds trans-13c, cis-13c/trans-13c (86:14), cis-15b/trans-15b (87:13) and trans-15d/cis-15d (95:5) exhibited the highest activity toward both TK and TK VZV strains (mean EC values in the range of 3.0-8.7 μM). The EC's for isoxazolidines trans-12a, cis-12a, cis-13a, trans-13d, cis-15a/trans-15a (50:50) ranged between 6.9 and 8.5 μM for VZV TK strain and between 10.7 and 13.2 μM for VZV TK strain. The isoxazolidine phosphonates cis-15/trans-15 having benzyl substituents both at N3 of the quinazoline-2,4-dione skeleton and at N2 of the isoxazolidine ring displayed some anti-cytomegalovirus potency but at the same time showed significant cytostatic activity for human embryonic lung fibroblasts (used to carry out the antiviral assays) as well as for other cell lines (i.e. CEM, L1210, HeLa and HMEC-1).

Authors : Piotrowska Dorota G, Andrei Graciela, Schols Dominique, Snoeck Robert, Łysakowska Magdalena,

(10) A highly conserved epitope-vaccine candidate against varicella-zoster virus induces neutralizing antibodies in mice.[TOP]

Pubmed ID :26873057
Publication Date : //
Varicella-zoster virus (VZV) is a highly infectious agent of varicella and herpes zoster (HZ). Vaccination is by far the most effective way to prevent these diseases. More safe, stable and efficient vaccines, such as epitope-based vaccines, now have been increasingly investigated by many researchers. However, only a few VZV neutralizing epitopes have been identified to date. We have previously identified a linear epitope between amino acid residues 121 and 135 of gE. In this study, we validated that this epitope is highly conserved amongst different VZV strains that covered five existing phylogenetic clades with an identity of 100%. We evaluated the immunogenicity of the recombinant hepatitis B virus core (HBc) virus-like particles (VLPs) which included amino acids (121-135). VZV-gE-specific antibodies were detected in immunized mouse serum using ELISA. The anti-peptide antiserum positively detected VZV via Western blot and immunofluorescent staining assays. More importantly, these peptides could neutralize VZV, indicating that these peptides represented neutralizing epitopes. These findings have important implications for the development of epitope-based protective VZV vaccines.

Authors : Zhu Rui, Liu Jian, Chen Chunye, Ye Xiangzhong, Xu Longfa, Wang Wei, Zhao Qinjian, Zhu Hua, Cheng Tong, Xia Ningshao,