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Sawsan Mahmoud, Hao Li, Tamara R McBrayer, Leda Bassit, Sherif F Hammad, Steven J Coats, Franck Amblard, Raymond F Schinazi
A novel series of tetrafluoro and hexafluoro acyclic nucleosides and their phosphoramidates were successfully prepared from commercially available 2,2,3,3-tetrafluoro-1,4-butanediol and 2,2,3,3,4,4-hexafluoro-1,5-pentanediol in four to six steps. Their ability to block HIV, HCV, HSV-1, and HBV replication along with their cytotoxicity toward HepG2, human lymphocyte, CEM, and Vero cells was assessed.
October 19, 2016: Nucleosides, Nucleotides & Nucleic Acids
Robert J Danaher, Derrick E Fouts, Agnes P Chan, Yongwook Choi, Jessica DePew, Jamison M McCorrison, Karen E Nelson, Chunmei Wang, Craig S Miller
Strain-specific factors contribute in significant but undefined ways to the variable incidence of herpes simplex virus (HSV) recrudescence. Studies that investigate these strain-specific factors are needed. Here, we used qPCR, in vitro assays, and genomic sequencing to identify important relationships between in vitro and clinical phenotypes of unique HSV-1 clinical isolates. Nine HSV-1 isolates from individuals displaying varying reactivation patterns were studied. Isolates associated with frequent recurrent herpes labialis (RHL) (1) displayed higher rates of viral shedding in the oral cavity than those associated with rare RHL and (2) tended to replicate more efficiently at 33 °C than 39 °C...
October 13, 2016: Journal of Neurovirology
Beyza Yavuz, Zafer Yazici
In this study, antiviral effect of porphyrin was investigated. Cooper strain of Bovine Herpes Virus type 1(BoHV-1) and Kos strain of Herpes Simplex Virus type-1 (HSV-1) were used to determine the potential of porphyrins to inhibit infection in vitro (with morphological and cytopathological criteria). Apoptotic and necrotic changes were determined by using DAPI and propidium staining. The non-cytotoxic dose of porphyrin (NCD-p) was initially calculated as 312.50µg/mL on MDBK and Vero cells. The apoptotic cell (APC) count was found 10% with BoHV-1 while it was 5...
September 2016: Pakistan Journal of Pharmaceutical Sciences
Fang Ma, Wenwei Shen, Xiaoqi Zhang, Manmei Li, Yifei Wang, Yuxiao Zou, Yaolan Li, Hui Wang
Six stilbene derivatives isolated from Mulberry leaves including Kuwanon X, Mulberrofuran C, Mulberrofuran G, Moracin C, Moracin M 3'-O-b-glucopyranoside and Moracin M were found to have antiviral effects against herpes simplex virus type 1 and 2 (HSV-1 and HSV-2) at different potencies except for Mulberrofuran G. Kuwanon X exhibited the greatest activity against HSV-1 15577 and clinical strains and HSV-2 strain 333 with IC50 values of 2.2, 1.5 and 2.5 µg/mL, respectively. Further study revealed that Kuwanon X did not inactivate cell-free HSV-1 particles, but inhibited cellular adsorption and penetration of HSV-1 viral particles...
2016: Biological & Pharmaceutical Bulletin
Chaolong Lin, Huanhuan Li, Mengru Hao, Dan Xiong, Yong Luo, Chenghao Huang, Quan Yuan, Jun Zhang, Ningshao Xia
Genetically modified HSV-1 viruses serve as promising vectors for tumour therapy and vaccine development. The CRISPR/Cas9 system is one of the most powerful tools for precise gene editing of the genomes of organisms. However, whether the CRISPR/Cas9 system can precisely and efficiently make gene replacements in the genome of HSV-1 remains essentially unknown. Here, we reported CRISPR/Cas9-mediated editing of the HSV-1 genome in human cells, including the knockout and replacement of large genes. In established cells stably expressing CRISPR/Cas9, gRNA in coordination with Cas9 could direct a precise cleavage within a pre-defined target region, and foreign genes were successfully used to replace the target gene seamlessly by HDR-mediated gene replacement...
October 7, 2016: Scientific Reports
Lynn M Hassman, David A DiLoreto
Herpes simplex virus 1 (HSV-1) is a nearly ubiquitous human pathogen, remaining dormant in its human host the majority of the time. The interaction between HSV-1 and the immune system represents a complicated balance of power that allows the virus to persist in the host for a lifetime. However, disruptions in the immune system can activate the virus with the potential to cause devastating infections in the central nervous system (CNS). We present a patient who suffered three consecutive yearly HSV-1 CNS episodes (encephalitis, seizure, and retinitis), each within days of his influenza vaccination...
2016: IDCases
Chunkui Zhou, Lijun Zhu, Shaokuan Fang
Herpes simplex virus (HSV) is the most common cause of acute viral encephalitis. Acute retinal necrosis (ARN) is a rapidly progressing and potentially blinding eye disease that may be induced by HSV. The present case study reports the very rare case of a patient with herpes simplex encephalitis (HSE) combined with acute retinal necrosis (ARN). A 47-year-old woman was admitted to hospital with persistent high fever and somnolence for 5 days. Magnetic resonance imaging showed abnormal signals in the right medial temporal lobes, and HSV-1 was identified in the serum and cerebrospinal fluid...
October 2016: Experimental and Therapeutic Medicine
D Topalis, S Gillemot, R Snoeck, G Andrei
Emergence of drug-resistance to all FDA-approved antiherpesvirus agents is an increasing concern in immunocompromised patients. Herpesvirus DNA polymerase (DNApol) is currently the target of nucleos(t)ide analogue-based therapy. Mutations in DNApol that confer resistance arose in immunocompromised patients infected with herpes simplex virus 1 (HSV-1) and human cytomegalovirus (HCMV), and to lesser extent in herpes simplex virus 2 (HSV-2), varicella zoster virus (VZV) and human herpesvirus 6 (HHV-6). In this review, we present distinct drug-resistant mutational profiles of herpesvirus DNApol...
September 29, 2016: Nucleic Acids Research
Nadia Martinez-Martin, Abel Viejo-Borbolla, Antonio Alcami
Herpes simplex virus type 1 and 2 (HSV-1 and HSV-2, respectively) are among the most prevalent human pathogens, causing a variety of diseases. HSV modulation of the chemokine network remains poorly understood. We have previously identified secreted glycoprotein G (gG) as the first viral chemokine binding protein that enhances chemokine function as a novel viral immunomodulatory mechanism. However, gG is also present at the viral envelope and its role in the virus particle remains unknown. Here we have addressed the chemokine binding capacity of HSV particles and the functionality of such interaction in vitro...
September 27, 2016: Journal of General Virology
Barbara Van Der Pol
HSV-1 and HSV-2 are among the most common causes of sexually transmitted infections (stis) globally. these infections are strongly associated with increased risk of hiv acquisition and rare, but devastating, neonatal disease. available treatment options can reduce HSV transmission and improve quality of life. accurate diagnosis early in disease can improve patient management. Areas covered: This paper describes the clinical manifestations of HSV infection often used for clinical diagnostic purposes. The paper then describes the evolution of laboratory diagnostic assays...
October 8, 2016: Expert Review of Molecular Diagnostics
Zhangtao Jiang, Chenhe Su, Chunfu Zheng
: The interferon-induced protein with tetratricopeptide repeats 3 (IFIT3 or ISG60) is a host intrinsic antiviral factor that restricts many DNA and RNA virus replication. Herpes simplex virus 1 (HSV-1), a DNA virus bearing a large genome, can encode many viral proteins to counteract the host immune responses. However, whether IFIT3 plays a role upon HSV-1 infection is little known. In this study, we show for the first time that HSV-1 tegument protein UL41, a viral endoribonuclease, plays an important role on inhibiting the antiviral activity of IFIT3...
September 28, 2016: Journal of Virology
Yi Zheng, Subodh Kumar Samrat, Haidong Gu
: Infected cell protein 0 (ICP0) of herpes simplex virus 1 (HSV-1) is an α gene product required for viral replication at low multiplicity of infection. Upon entry, nuclear domain 10 (ND10) converges at the incoming DNA and represses viral gene expression. ICP0 contains a RING-type E3 ubiquitin ligase, which degrades the ND10 organizer, PML, and disperses ND10 to alleviate the repression. In the present study, we focus on understanding the regulation on ICP0 E3 ligase activity in degrading different ICP0 substrates...
September 28, 2016: Journal of Virology
Jouliana Sadek, G Sullivan Read
: During lytic herpes simplex virus (HSV) infections, the virion host shutoff (Vhs) (UL41) endoribonuclease degrades many cellular and viral mRNAs. In uninfected cells, spliced mRNAs emerge into the cytoplasm bound by exon junction complexes (EJCs), and are translated several times more efficiently than unspliced mRNAs that have the same sequence, but lack EJCs. Notably, most cellular mRNAs are spliced, whereas most HSV mRNAs are not. To examine the effect of splicing on gene expression during an HSV infection, cells were transfected with plasmids encoding an unspliced renilla luciferase (RLuc) reporter mRNA, or RLuc constructs with introns near the 5' or 3' ends of the gene...
September 28, 2016: Journal of Virology
Zachary M Parker, Tracy Jo Pasieka, George A Parker, David A Leib
: The interferon (IFN) response to viral pathogens is critical for host survival. In humans and mouse models, defects in IFN responses can result in lethal herpes simplex type-1 (HSV-1) infections, usually from encephalitis. Although rare, HSV-1 can also cause fulminant hepatic failure which is often fatal. While herpes simplex encephalitis has been extensively studied, HSV-1 generalized infections and subsequent acute liver failure are less well understood. We previously demonstrated that IFNαβγR(-/-) mice are exquisitely susceptible to liver infection following corneal infection with HSV-1...
September 28, 2016: Journal of Virology
Hena Khalique, Jorge López Marco, Filip Lim
BACKGROUND: Although Herpes Simplex Virus Type 1 (HSV-1) has outstanding properties for gene delivery vectors and its genome is available in bacterial artificial chromosomes (BACs) for mutagenesis studies, one impediment is the presence of about 15.4 kilobases of DNA sequences which are duplicated in the HSV-1 genome, complicating vector construction and stability. METHODS: As a useful platform for building HSV-1 vectors, we have constructed a fully haploid HSV-1 genome BAC by deletion of one of these repeats, confirming that viral propagation in culture is not impaired...
September 27, 2016: Journal of Gene Medicine
Dr Mélanie Fromentin, Remy Gauzit, Benoit Gille, Charles Marc Samama
Genital herpes is increasingly caused by herpes simplex virus type 1 (HSV-1), but recurrences are less frequent than with HSV-2. Distinguishing between primary genital infection and reactivation can be difficult, but HSV-1 more often causes severe primary infections and fewer recurrences. However, as virus reactivation is common during septic shock, a severe form of HSV-1 reactivation can occur in locations other than the lungs, which remain the most common site. The case of a 79-year-old Caucasian man who presented with HSV-1 epididymo-orchitis after three episodes of severe sepsis or septic shock in the context of acute biliary necrotizing pancreatitis is described...
2016: IDCases
Meixin Chen, Qingcai Meng, Yunfei Qin, Puping Liang, Peng Tan, Lian He, Yubin Zhou, Yongjun Chen, Junjiu Huang, Rong-Fu Wang, Jun Cui
Cyclic GMP-AMP synthase (cGAS) is an essential DNA virus sensor that triggers type I interferon (IFN) signaling by producing cGAMP to initiate antiviral immunity. However, post-translational regulation of cGAS remains largely unknown. We report that K48-linked ubiquitination of cGAS is a recognition signal for p62-depdendent selective autophagic degradation. The induction of TRIM14 by type I IFN accelerates cGAS stabilization by recruiting USP14 to cleave the ubiquitin chains of cGAS at lysine (K) 414. Knockout of TRIM14 impairs herpes simplex virus type 1 (HSV-1)-triggered antiviral responses in a cGAS-dependent manner...
October 6, 2016: Molecular Cell
Jan Olsson, Hugo Lövheim, Emma Honkala, Pekka J Karhunen, Fredrik Elgh, Eloise H Kok
Herpes simplex virus (HSV) type 1 affects a majority of the population and recent evidence suggests involvement in Alzheimer's disease aetiology.We investigated HSV (1 and 2) prevalence in the Tampere Autopsy Study (TASTY) brain samples using PCR and sero-positivity in plasma, and associations with Alzheimer's disease neuropathology.HSV was shown to be present in human brain tissue in 11/584 (1.9%) of samples in the TASTY cohort, and 6 of those samples had Alzheimer's disease neuropathological amyloid beta (Aβ) aggregations...
September 23, 2016: Disease Models & Mechanisms
Muzammel Haque, Brent Stanfield, Konstantin G Kousoulas
We have previously shown that the HSV-1 gK and UL20 proteins interact and function in virion envelopment, membrane fusion, and neuronal entry. Alignment of the predicted secondary structures of gKs encoded by BoHV-1, HSV-1, HSV-2, EHV-1 and VZV indicated a high degree of domain conservation. Two BoHV-1 gK-null mutant viruses were created by either gK gene deletion or stop codon insertion. In addition, a V5 epitope-tag was inserted at the carboxyl terminus of gK gene to detect gK. The engineered gK-null mutant viruses failed to replicate and produce viral plaques...
September 20, 2016: Virology
Larissa Fonseca da Cunha Sousa, Milene Alvarenga Rachid, Graciela Kunrath Lima, Aline Silva de Miranda, Márcia de Carvalho Vilela, Norinne Lacerda Queiroz, David Henrique Rodrigues, Marco Antonio Campos, Erna Geessien Kroon, Fabiana Simão Machado, Antônio Lúcio Teixeira
The most severe manifestation of Herpes Simplex Type 1 virus (HSV-1) infection is encephalitis characterized by arousal impairment and seizures that can evolve to coma and death. Previous studies reported the involvement of suppressor of cytokine signaling (SOCS) proteins, specifically SOCS1 and SOCS3, in HSV-1 infection, suggesting that other members of this family could be involved in the immune response against HSV-1. No previous study has reported the role of SOCS2 in HSV-1 infection. In the current study, C57BL/6 wild-type mice (WT) and mice deficient in SOCS2 gene (SOCS2(-/-)) were subjected to intracranial inoculation with 10(2) plaque forming units (PFU) of HSV-1...
September 16, 2016: Brain Research Bulletin
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