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https://www.readbyqxmd.com/read/28433053/the-envelope-proteins-of-the-bunyavirales
#1
Pablo Guardado-Calvo, Félix A Rey
The Bunyavirales Order encompasses nine families of enveloped viruses containing a single-stranded negative-sense RNA genome divided into three segments. The small (S) and large (L) segments encode proteins participating in genome replication in the infected cell cytoplasm. The middle (M) segment encodes the viral glycoproteins Gn and Gc, which are derived from a precursor polyprotein by host cell proteases. Entry studies are available only for a few viruses in the Order, and in each case they were shown to enter cells via receptor-mediated endocytosis...
2017: Advances in Virus Research
https://www.readbyqxmd.com/read/28432926/tick-borne-encephalitis-virus-infects-human-brain-microvascular-endothelial-cells-without-compromising-blood-brain-barrier-integrity
#2
Martin Palus, Marie Vancova, Jana Sirmarova, Jana Elsterova, Jan Perner, Daniel Ruzek
Alteration of the blood-brain barrier (BBB) is a hallmark of tick-borne encephalitis (TBE), a life-threating human viral neuroinfection. However, the mechanism of BBB breakdown during TBE, as well as TBE virus (TBEV) entry into the brain is unclear. Here, primary human microvascular endothelial cells (HBMECs) were infected with TBEV to study interactions with the BBB. Although the number of infected cells was relatively low in culture (<5%), the infection was persistent with high TBEV yields (>10(6)pfu/ml)...
April 19, 2017: Virology
https://www.readbyqxmd.com/read/28428548/antiviral-activities-of-schizonepeta-tenuifolia-briq-against-enterovirus-71-in-vitro-and-in-vivo
#3
Sin-Guang Chen, Mei-Ling Cheng, Kuan-Hsing Chen, Jim-Tong Horng, Ching-Chuan Liu, Shih-Min Wang, Hiroaki Sakurai, Yann-Lii Leu, Shulhn-Der Wang, Hung-Yao Ho
No effective drug is currently available for treatment of enterovirus 71 (EV71) infection. Schizonepeta tenuifolia Briq. (ST) has been used as a herbal constituent of traditional Chinese medicine. We studied whether the aqueous extract of Schizonepeta tenuifolia Briq (STE) has antiviral activity. STE inhibited replication of EV71, as evident by its ability to diminish plaque formation and cytopathic effect induced by EV71, and to inhibit the synthesis of viral RNA and protein. Moreover, daily single-dose STE treatment significantly improved the survival of EV71-infected mice, and ameliorated the symptoms...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28428345/proliferation-of-primary-human-hepatocytes-and-prevention-of-hepatitis-b-virus-reinfection-efficiently-deplete-nuclear-cccdna-in-vivo
#4
Lena Allweiss, Tassilo Volz, Katja Giersch, Janine Kah, Giuseppina Raffa, Joerg Petersen, Ansgar W Lohse, Concetta Beninati, Teresa Pollicino, Stephan Urban, Marc Lütgehetmann, Maura Dandri
OBJECTIVE: The stability of the covalently closed circular DNA (cccDNA) in nuclei of non-dividing hepatocytes represents a key determinant of HBV persistence. Contrarily, studies with animal hepadnaviruses indicated that hepatocyte turnover can reduce cccDNA loads but knowledge on the proliferative capacity of HBV-infected primary human hepatocytes (PHHs) in vivo and the fate of cccDNA in dividing PHHs is still lacking. This study aimed to determine the impact of human hepatocyte division on cccDNA stability in vivo...
April 20, 2017: Gut
https://www.readbyqxmd.com/read/28423319/tam-receptors-are-not-required-for-zika-virus-infection-in-mice
#5
Andrew K Hastings, Laura J Yockey, Brett W Jagger, Jesse Hwang, Ryuta Uraki, Hallie F Gaitsch, Lindsay A Parnell, Bin Cao, Indira U Mysorekar, Carla V Rothlin, Erol Fikrig, Michael S Diamond, Akiko Iwasaki
Tyro3, Axl, and Mertk (TAM) receptors are candidate entry receptors for infection with the Zika virus (ZIKV), an emerging flavivirus of global public health concern. To investigate the requirement of TAM receptors for ZIKV infection, we used several routes of viral inoculation and compared viral replication in wild-type versus Axl(-/-), Mertk(-/-), Axl(-/-)Mertk(-/-), and Axl(-/-)Tyro3(-/-) mice in various organs. Pregnant and non-pregnant mice treated with interferon-α-receptor (IFNAR)-blocking (MAR1-5A3) antibody and infected subcutaneously with ZIKV showed no reliance on TAMs for infection...
April 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28423057/insertion-of-a-ligand-to-her2-in-gb-retargets-hsv-tropism-and-obviates-the-need-for-activation-of-the-other-entry-glycoproteins
#6
Biljana Petrovic, Tatiana Gianni, Valentina Gatta, Gabriella Campadelli-Fiume
Herpes simplex virus (HSV) entry into the cells requires glycoproteins gD, gH/gL and gB, activated in a cascade fashion by conformational modifications induced by cognate receptors and intermolecular signaling. The receptors are nectin1 and HVEM (Herpes virus entry mediator) for gD, and αvβ6 or αvβ8 integrin for gH. In earlier work, insertion of a single chain antibody (scFv) to the cancer receptor HER2 (human epidermal growth factor receptor 2) in gD, or in gH, resulted in HSVs specifically retargeted to the HER2-positive cancer cells, hence in highly specific non-attenuated oncolytic agents...
April 19, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28422787/how-hiv-1-entry-mechanism-and-broadly-neutralizing-antibodies-guide-structure-based-vaccine-design
#7
Marie Pancera, Anita Changela, Peter D Kwong
PURPOSE OF REVIEW: An HIV-1 vaccine that elicits broadly neutralizing antibodies (bNAbs) remains to be developed. Here, we review how knowledge of bNAbs and HIV-1 entry mechanism is guiding the structure-based design of vaccine immunogens and immunization regimens. RECENT FINDINGS: Isolation of bNAbs from HIV-1-infected donors has led to an unprecedented understanding of the sites of vulnerability that these antibodies target on the HIV-1 envelope (Env) as well as of the immunological pathways that these antibody lineages follow to develop broad and potent neutralization...
May 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28420742/synergistic-internal-ribosome-entry-site-microrna-based-approach-for-flavivirus-attenuation-and-live-vaccine-development
#8
Konstantin A Tsetsarkin, Guangping Liu, Evgeniya Volkova, Alexander G Pletnev
The recent emergence of Zika virus underscores the need for new strategies for a rapid development of safe flavivirus vaccines. Using another flavivirus (Langat virus [LGTV]) that belongs to the group of tick-borne flaviviruses as a model, we describe a dual strategy for virus attenuation which synergistically accesses the specificity of microRNA (miRNA) genome targeting and the effectiveness of internal ribosome entry site (IRES) insertion. To increase the stability and immunogenicity of bicistronic LGTVs, we developed a novel approach in which the capsid (C) protein gene was relocated into the 3' noncoding region (NCR) and expressed under translational control from an IRES...
April 18, 2017: MBio
https://www.readbyqxmd.com/read/28416666/drebrin-restricts-rotavirus-entry-by-inhibiting-dynamin-mediated-endocytosis
#9
Bin Li, Siyuan Ding, Ningguo Feng, Nancie Mooney, Yaw Shin Ooi, Lili Ren, Jonathan Diep, Marcus R Kelly, Linda L Yasukawa, John T Patton, Hiroyuki Yamazaki, Tomoaki Shirao, Peter K Jackson, Harry B Greenberg
Despite the wide administration of several effective vaccines, rotavirus (RV) remains the single most important etiological agent of severe diarrhea in infants and young children worldwide, with an annual mortality of over 200,000 people. RV attachment and internalization into target cells is mediated by its outer capsid protein VP4. To better understand the molecular details of RV entry, we performed tandem affinity purification coupled with high-resolution mass spectrometry to map the host proteins that interact with VP4...
April 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28411453/inhibition-of-influenza-virus-infection-by-multivalent-pentacyclic-triterpene-functionalized-per-o-methylated-cyclodextrin-conjugates
#10
Zhenyu Tian, Longlong Si, Kun Meng, Xiaoshu Zhou, Yongmin Zhang, Demin Zhou, Sulong Xiao
Multivalent ligands that exhibit high binding affinity to influenza hemagglutinin (HA) trimer can block the interaction of HA with its sialic acid receptor. In this study, a series of multivalent pentacyclic triterpene-functionalized per-O-methylated cyclodextrin (CD) derivatives were designed and synthesized using 1, 3-dipolar cycloaddition click reaction. A cell-based assay showed that three compounds (25, 28 and 31) exhibited strong inhibitory activity against influenza A/WSN/33 (H1N1) virus. Compound 28 showed the most potent anti-influenza activity with IC50 of 4...
April 2, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28410420/comparison-of-cell-based-assays-for-the-identification-and-evaluation-of-competitive-cxcr4-inhibitors
#11
Anneleen Van Hout, Thomas D'huys, Merel Oeyen, Dominique Schols, Tom Van Loy
The chemokine receptor CXCR4 is activated by its unique chemokine ligand CXCL12 and regulates many physiological and developmental processes such as hematopoietic cell trafficking. CXCR4 is also one of the main co-receptors for human immunodeficiency virus (HIV) entry. Dysfunction of the CXCL12/CXCR4 axis contributes to several human pathologies, including cancer and inflammatory diseases. Consequently, inhibition of CXCR4 activation is recognized as an attractive target for therapeutic intervention. In this regard, numerous agents modifying CXCR4 activity have been evaluated in in vitro experimental studies and pre-clinical models...
2017: PloS One
https://www.readbyqxmd.com/read/28409676/analysis-of-risk-factors-for-persistent-infection-of-asymptomatic-women-with-high-risk-human-papilloma-virus
#12
Nianmin Shi, Qiang Lu, Jiao Zhang, Li Li, Junnan Zhang, Fanglei Zhang, Yanhong Dong, Xinyue Zhang, Zheng Zhang
OBJECTIVE: This study aims to prevent persistent infection, reduce the incidence of cervical cancer, and improve women's health by understanding the theoretical basis of the risk factors for continuous infection of asymptomatic women with high-risk human papilloma virus (HPV) strains via information collected, which includes the persistent infection rate and the most prevalent HPV strain types of high risk to asymptomatic women in the high-risk area of cervical cancer in Linfen, Shanxi Province...
April 14, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28407288/efficient-replication-of-blood-borne-hepatitis-c-virus-in-human-fetal-liver-stem-cells
#13
Xuan Guo, Shu Wang, Zhi-Gang Qiu, Ya-Ling Dou, Wei-Li Liu, Dong Yang, Zhi-Qiang Shen, Zhao-Li Chen, Jing-Feng Wang, Bin- Zhang, Xin-Wei Wang, Xiang-Fei Guo, Xue-Lian Zhang, Min Jin, Jun-Wen Li
The development of pathogenic mechanisms, specific antiviral treatments and preventive vaccines for hepatitis C virus (HCV) infection has been limited due to lack of cell culture model that could naturally imitate the entire HCV life cycle. Here, we established a HCV cell culture model based on human fetal liver stem cells (hFLSCs) that supports the entire blood-borne hepatitis C virus (bbHCV) life cycle. More than 90% of cells remained infected by various genotypes. bbHCV was efficiently propagated, and progeny virus were infectious to hFLSCs...
April 13, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28406138/inhibition-of-endocytic-pathways-impacts-cytomegalovirus-maturation
#14
Madeline A Archer, Teal M Brechtel, Leslie E Davis, Rinkuben C Parmar, Mohammad H Hasan, Ritesh Tandon
Endocytic processes are critical for cellular entry of several viruses; however, the role of endocytosis in cellular trafficking of viruses beyond virus entry is only partially understood. Here, we utilized two laboratory strains (AD169 and Towne) of human cytomegalovirus (HCMV), which are known to use cell membrane fusion rather than endocytosis to enter fibroblasts, in order to study a post-entry role of endocytosis in HCMV life cycle. Upon pharmacological inhibition of dynamin-2 or clathrin terminal domain (TD) ligand association, these strains entered the cells successfully based on the expression of immediate early viral protein...
April 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28406093/antiviral-activity-of-nobiletin-against-chikungunya-virus-in-vitro
#15
Shih-Chao Lin, Mei-Chun Chen, Shiming Li, Chi-Chen Lin, Tony T Wang
BACKGROUND: Chikungunya virus (CHIKV), a highly contagious re-emerging virus, is transmitted by infected mosquitoes. CHIKV is prevalent in tropical countries and is continuing to creep farther north into temperate areas. CHIKV is responsible for induction of Chikungunya Fever (CF) and severe joint stiffness with the capability of developing into bilateral and systemic arthralgia or even encephalitis. Despite the high morbidity rate, no approved antiviral drug is available. Therefore, an anti-CHIKV therapy is necessary to control this disease...
April 13, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28405607/chemoattractant-mediated-leukocyte-trafficking-enables-hiv-dissemination-from-the-genital-mucosa
#16
Maud Deruaz, Thomas T Murooka, Sophina Ji, Marc A Gavin, Vladimir D Vrbanac, Judy Lieberman, Andrew M Tager, Thorsten R Mempel, Andrew D Luster
HIV vaginal transmission accounts for the majority of newly acquired heterosexual infections. However, the mechanism by which HIV spreads from the initial site of viral entry at the mucosal surface of the female genital tract to establish a systemic infection of lymphoid and peripheral tissues is not known. Once the virus exits the mucosa it rapidly spreads to all tissues, leading to CD4(+) T cell depletion and the establishment of a viral reservoir that cannot be eliminated with current treatments. Understanding the molecular and cellular requirements for viral dissemination from the genital tract is therefore of great importance, as it could reveal new strategies to lengthen the window of opportunity to target the virus at its entry site in the mucosa where it is the most vulnerable and thus prevent systemic infection...
April 6, 2017: JCI Insight
https://www.readbyqxmd.com/read/28404899/balb-c-mice-immunized-with-a-combination-of-virus-like-particles-incorporating-kaposi-sarcoma-associated-herpesvirus-kshv-envelope-glycoproteins-gpk8-1-gb-and-gh-gl-induced-comparable-serum-neutralizing-antibody-activity-to-uv-inactivated-kshv
#17
Anne K Barasa, Peng Ye, Meredith Phelps, Ganapathiram T Arivudainambi, Timelia Tison, Javier Gordon Ogembo
Infection with Kaposi sarcoma-associated herpesvirus (KSHV) is estimated to account for over 44,000 new cases of Kaposi sarcoma annually, with 84% occurring in Africa, where the virus is endemic. To date, there is no prophylactic vaccine against KSHV. KSHV gpK8.1, gB, and gH/gL glycoproteins, implicated in the virus entry into host cells, are attractive vaccine targets for eliciting potent neutralizing antibodies (nAbs) against virus infection. We incorporated gpK8.1, gB, or gH/gL on the surface of virus-like particles (VLPs) and characterized these VLPs for their composition, size, and functionality...
February 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28404852/attachment-and-post-attachment-receptors-important-for-hepatitis-c-virus-infection-and-cell-to-cell-transmission
#18
Huahao Fan, Luhua Qiao, Kyung-Don Kang, Junfen Fan, Wensheng Wei, Guangxiang Luo
Hepatitis C virus (HCV) infection requires multiple receptors for its attachment and entry to the cell. Our previous studies found that human syndecan-1 (SDC-1), SDC-2, and T cell immunoglobulin and mucin domain-containing protein 1 (TIM-1) are HCV attachment receptors. Other cell surface molecules such as CD81, CLDN1, OCLN, SR-BI, and LDLR mainly function at post-attachment steps, which are considered post-attachment receptors. The underlying molecular mechanisms of different receptors in HCV cell-free and cell-to-cell transmission remain elusive...
April 12, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28404849/quantitative-proteomic-analysis-of-mosquito-c6-36-cells-reveals-host-proteins-involved-in-zika-virus-infection
#19
Qi-Lin Xin, Cheng-Lin Deng, Xi Chen, Jun Wang, Shao-Bo Wang, Wei Wang, Fei Deng, Bo Zhang, Gengfu Xiao, Lei-Ke Zhang
Zika virus (ZIKV) is an emerging arbovirus belonging to the genus Flavivirus of the family Flaviviridae During replication processes, flavivirus will manipulate host cell systems to facilitate their replication, while the host cells will activate antiviral responses. Identification of host proteins involved in flavivirus replication process may lead to the discovery of antiviral targets. Mosquito Aedes aegypti and Aedes albopictus are epidemiologically important vectors for ZIKV, and effective restrictions of ZIKV replication in mosquitoes will be vital in controlling the spread of virus...
April 12, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28403220/a-derivative-of-platelet-derived-growth-factor-receptor-alpha-binds-to-the-trimer-of-human-cytomegalovirus-and-inhibits-entry-into-fibroblasts-and-endothelial-cells
#20
Cora Stegmann, Daniel Hochdorfer, Diana Lieber, Narmadha Subramanian, Dagmar Stöhr, Kerstin Laib Sampaio, Christian Sinzger
Human cytomegalovirus (HCMV) is a widely distributed herpesvirus that causes significant morbidity in immunocompromised hosts. Inhibitors of viral DNA replication are available, but adverse effects limit their use. Alternative antiviral strategies may include inhibition of entry. We show that soluble derivatives of the platelet-derived growth factor receptor alpha (PDGFR-alpha), a putative receptor of HCMV, can inhibit HCMV infection of various cell types. A PDGFR-alpha-Fc fusion protein binds to and neutralizes cell-free virus particles at an EC50 of 10-30 ng/ml...
April 2017: PLoS Pathogens
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