Rabies leviää Libanonissa pakolaisleiriolosuhteiden jatkuessa

Muistiin 24.2.2018

http://www.dailystar.com.lb/News/Lebanon-News/2018/Feb-24/439191-hasbani-links-rabies-spike-to-refugee-influx.ashx

Concerning Travellers to Lebanon:

Rabies can be found in dogs, bats, and other mammals in Lebanon, so CDC recommends this vaccine for the following groups:

• Travelers involved in outdoor and other activities (such as camping, hiking, biking, adventure travel, and caving) that put them at risk for animal bites.
• People who will be working with or around animals (such as veterinarians, wildlife professionals, and researchers).
• People who are taking long trips or moving to Lebanon
• Children, because they tend to play with animals, might not report bites, and are more likely to have animal bites on their head and neck.
  

Ps. 89:15,16

6.2.2018,10:12.Sana psalmista 86:15,16.

(A Maskil of Ethan the Ezrahite) Blessed are the people who know the festal shout, who walk , o Lord, in the light of thy countenance.who exult in thy name all the day, and extol thy righteousness.

Uutta Pathogeeneista. otsikoita 2.2. 2018

 http://journals.plos.org/plospathogens/issue

Opinions

The curious case of APOBEC3 activation by cancer-associated human papillomaviruses

Nicholas A. Wallace, Karl Münger

PLOS Pathogens: published January 11, 2018 | https://doi.org/10.1371/journal.ppat.1006717

Although it's painful: The importance of stringent antibody validation

Victoria A. Meliopoulos, Stacey Schultz-Cherry

PLOS Pathogens: published January 4, 2018 | https://doi.org/10.1371/journal.ppat.1006701

Pearls

Does nonreproductive swarming adapt to pathogens?

Qingyun Diao, Chunsheng Hou

PLOS Pathogens: published January 25, 2018 | https://doi.org/10.1371/journal.ppat.1006742

The oral microbiome: A Lesson in coexistence

Ahmed S. Sultan, Eric F. Kong, Alexandra M. Rizk, Mary Ann Jabra-Rizk

PLOS Pathogens: published January 25, 2018 | https://doi.org/10.1371/journal.ppat.1006719

Habits of a highly successful cereal killer, Striga

Steven Runo, Eric K. Kuria

PLOS Pathogens: published January 11, 2018 | https://doi.org/10.1371/journal.ppat.1006731

Chaperone functional specificity promotes yeast prion diversity

Andrea N. Killian, Justin K. Hines

PLOS Pathogens: published January 4, 2018 | https://doi.org/10.1371/journal.ppat.1006695

From phagocytosis to metaforosis: Calcineurin’s deadly role in innate processing of fungi

Darius Armstrong-James, Leon de Boer, Amelia Bercusson, Anand Shah

PLOS Pathogens: published January 4, 2018 | https://doi.org/10.1371/journal.ppat.1006627

Review

Tissue-specific transcriptome analyses provide new insights into GPCR signalling in adult Schistosoma mansoni

Steffen Hahnel, Nic Wheeler, Zhigang Lu, Arporn Wangwiwatsin, Paul McVeigh, Aaron Maule, Matthew Berriman, Timothy Day, Paula Ribeiro, Christoph G. Grevelding

PLOS Pathogens: published January 18, 2018 | https://doi.org/10.1371/journal.ppat.1006718

Research Articles

The fungal pathogen Magnaporthe oryzae suppresses innate immunity by modulating a host potassium channel

Xuetao Shi, Yu Long, Feng He, Chongyang Zhang, Ruyi Wang, Ting Zhang, Wei Wu, Zeyun Hao, Yi Wang, Guo-Liang Wang, Yuese Ning

PLOS Pathogens: published January 31, 2018 | https://doi.org/10.1371/journal.ppat.1006878

Recombinant PrP^Sc shares structural features with brain-derived PrP^Sc: Insights from limited proteolysis

Alejandro M. Sevillano, Natalia Fernández-Borges, Neelam Younas, Fei Wang, Saioa R. Elezgarai, Susana Bravo, Ester Vázquez-Fernández, Isaac Rosa, Hasier Eraña, David Gil, Sonia Veiga, Enric Vidal, Melissa L. Erickson-Beltran, Esteban Guitián, Christopher J. Silva, Romolo Nonno, Jiyan Ma, Joaquín Castilla, Jesús R. Requena

PLOS Pathogens: published January 31, 2018 | https://doi.org/10.1371/journal.ppat.1006797

A new mechanism of interferon’s antiviral action: Induction of autophagy, essential for paramyxovirus replication, is inhibited by the interferon stimulated gene, TDRD7

Gayatri Subramanian, Teodora Kuzmanovic, Ying Zhang, Cara Beate Peter, Manoj Veleeparambil, Ritu Chakravarti, Ganes C. Sen, Saurabh Chattopadhyay

PLOS Pathogens: published January 30, 2018 | https://doi.org/10.1371/journal.ppat.1006877

The Xanthomonas euvesicatoria type III effector XopAU is an active protein kinase that manipulates plant MAP kinase signaling

Doron Teper, Anil Madhusoodana Girija, Eran Bosis, Georgy Popov, Alon Savidor, Guido Sessa

PLOS Pathogens: published January 29, 2018 | https://doi.org/10.1371/journal.ppat.1006880

Human cytomegalovirus UL23 inhibits transcription of interferon-γ stimulated genes and blocks antiviral interferon-γ responses by interacting with human N-myc interactor protein

Linyuan Feng, Jingxue Sheng, Gia-Phong Vu, Yujun Liu, Chingman Foo, Songbin Wu, Phong Trang, Marco Paliza-Carre, Yanhong Ran, Xiaoping Yang, Xu Sun, Zemin Deng, Tianhong Zhou, Sangwei Lu, Hongjian Li, Fenyong Liu

PLOS Pathogens: published January 29, 2018 | https://doi.org/10.1371/journal.ppat.1006867

Attenuation of a very virulent Marek's disease herpesvirus (MDV) by codon pair bias deoptimization

Kathrin Eschke, Jakob Trimpert, Nikolaus Osterrieder, Dusan Kunec

PLOS Pathogens: published January 29, 2018 | https://doi.org/10.1371/journal.ppat.1006857

Alphavirus-induced hyperactivation of PI3K/AKT directs pro-viral metabolic changes

Michela Mazzon, Cecilia Castro, Bastian Thaa, Lifeng Liu, Margit Mutso, Xiang Liu, Suresh Mahalingam, Julian L. Griffin, Mark Marsh, Gerald M. McInerney

PLOS Pathogens: published January 29, 2018 | https://doi.org/10.1371/journal.ppat.1006835

Global synonymous mutagenesis identifies cis-acting RNA elements that regulate HIV-1 splicing and replication

Matthew Takata, Steven J. Soll, Ann Emery, Daniel Blanco-Melo, Ronald Swanstrom, Paul D. Bieniasz

PLOS Pathogens: published January 29, 2018 | https://doi.org/10.1371/journal.ppat.1006824

Lipid droplet formation in Mycobacterium tuberculosis infected macrophages requires IFN-γ/HIF-1α signaling and supports host defense

Matthew Knight, Jonathan Braverman, Kaleb Asfaha, Karsten Gronert, Sarah Stanley

PLOS Pathogens: published January 25, 2018 | https://doi.org/10.1371/journal.ppat.1006874

Intracellular trafficking of begomoviruses in the midgut cells of their insect vector

Wen-Qiang Xia, Yan Liang, Yao Chi, Li-Long Pan, Jing Zhao, Shu-Sheng Liu, Xiao-Wei Wang

PLOS Pathogens: published January 25, 2018 | https://doi.org/10.1371/journal.ppat.1006866

Two closely related Rho GTPases, Cdc42 and RacA, of the en-dophytic fungus Epichloë festucae have contrasting roles for ROS production and symbiotic infection synchronized with the host plant

Yuka Kayano, Aiko Tanaka, Daigo Takemoto

PLOS Pathogens: published January 25, 2018 | https://doi.org/10.1371/journal.ppat.1006840

MERS-CoV 4b protein interferes with the NF-κB-dependent innate immune response during infection

Javier Canton, Anthony R. Fehr, Raúl Fernandez-Delgado, Francisco J. Gutierrez-Alvarez, Maria T. Sanchez-Aparicio, Adolfo García-Sastre, Stanley Perlman, Luis Enjuanes, Isabel Sola

PLOS Pathogens: published January 25, 2018 | https://doi.org/10.1371/journal.ppat.1006838

Phenotypic deficits in the HIV-1 envelope are associated with the maturation of a V2-directed broadly neutralizing antibody lineage

Lucia Reh, Carsten Magnus, Claus Kadelka, Denise Kühnert, Therese Uhr, Jacqueline Weber, Lynn Morris, Penny L. Moore, Alexandra Trkola

PLOS Pathogens: published January 25, 2018 | https://doi.org/10.1371/journal.ppat.1006825

The Wolbachia strain wAu provides highly efficient virus transmission blocking in Aedes aegypti

Thomas H. Ant, Christie S. Herd, Vincent Geoghegan, Ary A. Hoffmann, Steven P. Sinkins

PLOS Pathogens: published January 25, 2018 | https://doi.org/10.1371/journal.ppat.1006815

Alterations of HIV-1 envelope phenotype and antibody-mediated neutralization by signal peptide mutations

Chitra Upadhyay, Roya Feyznezhad, Weiming Yang, Hui Zhang, Susan Zolla-Pazner, Catarina E. Hioe

PLOS Pathogens: published January 25, 2018 | https://doi.org/10.1371/journal.ppat.1006812

Conditional mutagenesis in vivo reveals cell type- and infection stage-specific requirements for LANA in chronic MHV68 infection

Eduardo Salinas, Arundhati Gupta, Jeffrey M. Sifford, Darby G. Oldenburg, Douglas W. White, J. Craig Forrest

PLOS Pathogens: published January 24, 2018 | https://doi.org/10.1371/journal.ppat.1006865

The structure of FIV reverse transcriptase and its implications for non-nucleoside inhibitor resistance

Meytal Galilee, Akram Alian

PLOS Pathogens: published January 24, 2018 | https://doi.org/10.1371/journal.ppat.1006849

Cathepsin B aggravates coxsackievirus B3-induced myocarditis through activating the inflammasome and promoting pyroptosis

Yaping Wang, Liangliang Jia, Jian Shen, Yidong Wang, Zurong Fu, Sheng-an Su, Zhejun Cai, Jian-an Wang, Meixiang Xiang

PLOS Pathogens: published January 23, 2018 | https://doi.org/10.1371/journal.ppat.1006872

Interferon regulatory factor 8 regulates caspase-1 expression to facilitate Epstein-Barr virus reactivation in response to B cell receptor stimulation and chemical induction

Dong-Wen Lv, Kun Zhang, Renfeng Li

PLOS Pathogens: published January 22, 2018 | https://doi.org/10.1371/journal.ppat.1006868

Infectious blood source alters early foregut infection and regurgitative transmission of Yersinia pestis by rodent fleas

David M. Bland, Clayton O. Jarrett, Christopher F. Bosio, B. Joseph Hinnebusch

PLOS Pathogens: published January 22, 2018 | https://doi.org/10.1371/journal.ppat.1006859

Herpesvirus deconjugases inhibit the IFN response by promoting TRIM25 autoubiquitination and functional inactivation of the RIG-I signalosome

Soham Gupta, Päivi Ylä-Anttila, Simone Callegari, Ming-Han Tsai, Henri-Jacques Delecluse, Maria G. Masucci

PLOS Pathogens: published January 22, 2018 | https://doi.org/10.1371/journal.ppat.1006852

Identification of a novel protein complex essential for effector translocation across the parasitophorous vacuole membrane of Toxoplasma gondii

Nicole D. Marino, Michael W. Panas, Magdalena Franco, Terence C. Theisen, Adit Naor, Suchita Rastogi, Kerry R. Buchholz, Hernan A. Lorenzi, John C. Boothroyd

PLOS Pathogens: published January 22, 2018 | https://doi.org/10.1371/journal.ppat.1006828

The fungal myosin I is essential for Fusarium toxisome formation

Guangfei Tang, Yun Chen, Jin-Rong Xu, H. Corby Kistler, Zhonghua Ma

PLOS Pathogens: published January 22, 2018 | https://doi.org/10.1371/journal.ppat.1006827

Regional and subtype-dependent miRNA signatures in sporadic Creutzfeldt-Jakob disease are accompanied by alterations in miRNA silencing machinery and biogenesis

Franc Llorens, Katrin Thüne, Eulàlia Martí, Eirini Kanata, Dimitra Dafou, Daniela Díaz-Lucena, Ana Vivancos, Orr Shomroni, Saima Zafar, Matthias Schmitz, Uwe Michel, Natalia Fernández-Borges, Olivier Andréoletti, José Antonio del Río, Juana Díez, Andre Fischer, Stefan Bonn, Theodoros Sklaviadis, Juan Maria Torres, Isidre Ferrer, Inga Zerr

PLOS Pathogens: published January 22, 2018 | https://doi.org/10.1371/journal.ppat.1006802

Phospholipid scramblase 1 interacts with influenza A virus NP, impairing its nuclear import and thereby suppressing virus replication

Weiyu Luo, Jie Zhang, Libin Liang, Guangwen Wang, Qibing Li, Pengyang Zhu, Yuan Zhou, Junping Li, Yuhui Zhao, Nan Sun, Shanyu Huang, Chenchen Zhou, Yu Chang, Pengfei Cui, Pucheng Chen, Yongping Jiang, Guohua Deng, Zhigao Bu, Chengjun Li, Li Jiang, Hualan Chen

PLOS Pathogens: published January 19, 2018 | https://doi.org/10.1371/journal.ppat.1006851

Bunyavirus requirement for endosomal K⁺ reveals new roles of cellular ion channels during infection

Samantha Hover, Becky Foster, Juan Fontana, Alain Kohl, Steve A. N. Goldstein, John N. Barr, Jamel Mankouri

PLOS Pathogens: published January 19, 2018 | https://doi.org/10.1371/journal.ppat.1006845

RNA-Seq of Kaposi’s sarcoma reveals alterations in glucose and lipid metabolism

For Yue Tso, Andrew V. Kossenkov, Salum J. Lidenge, Owen Ngalamika, John R. Ngowi, Julius Mwaiselage, Jayamanna Wickramasinghe, Eun Hee Kwon, John T. West, Paul M. Lieberman, Charles Wood

PLOS Pathogens: published January 19, 2018 | https://doi.org/10.1371/journal.ppat.1006844

A role for domain I of the hepatitis C virus NS5A protein in virus assembly

Chunhong Yin, Niluka Goonawardane, Hazel Stewart, Mark Harris

PLOS Pathogens: published January 19, 2018 | https://doi.org/10.1371/journal.ppat.1006834

IFNγ inhibits G-CSF induced neutrophil expansion and invasion of the CNS to prevent viral encephalitis

Chandran Ramakrishna, Edouard M. Cantin

PLOS Pathogens: published January 19, 2018 | https://doi.org/10.1371/journal.ppat.1006822

Activation of PI3K, Akt, and ERK during early rotavirus infection leads to V-ATPase-dependent endosomal acidification required for uncoating

Mahmoud Soliman, Ja-Young Seo, Deok-Song Kim, Ji-Yun Kim, Jun-Gyu Park, Mia Madel Alfajaro, Yeong-Bin Baek, Eun-Hyo Cho, Joseph Kwon, Jong-Soon Choi, Mun-Il Kang, Sang-Ik Park, Kyoung-Oh Cho

PLOS Pathogens: published January 19, 2018 | https://doi.org/10.1371/journal.ppat.1006820

Leishmania proteophosphoglycans regurgitated from infected sand flies accelerate dermal wound repair and exacerbate leishmaniasis via insulin-like growth factor 1-dependent signalling

Emilie Giraud, Tereza Lestinova, Tamsyn Derrick, Oihane Martin, Rod J. Dillon, Petr Volf, Ingrid Műller, Paul A. Bates, Matthew E. Rogers

PLOS Pathogens: published January 19, 2018 | https://doi.org/10.1371/journal.ppat.1006794

Decoding the network of Trypanosoma brucei proteins that determines sensitivity to apolipoprotein-L1

Rachel B. Currier, Anneli Cooper, Hollie Burrell-Saward, Annette MacLeod, Sam Alsford

PLOS Pathogens: published January 18, 2018 | https://doi.org/10.1371/journal.ppat.1006855

Initial acquisition and succession of the cystic fibrosis lung microbiome is associated with disease progression in infants and preschool children

Marianne S. Muhlebach, Bryan T. Zorn, Charles R. Esther, Joseph E. Hatch, Conor P. Murray, Lidija Turkovic, Sarath C. Ranganathan, Richard C. Boucher, Stephen M. Stick, Matthew C. Wolfgang

PLOS Pathogens: published January 18, 2018 | https://doi.org/10.1371/journal.ppat.1006798

Influenza A virus hemagglutinin glycosylation compensates for antibody escape fitness costs

Ivan Kosik, William L. Ince, Lauren E. Gentles, Andrew J. Oler, Martina Kosikova, Matthew Angel, Javier G. Magadán, Hang Xie, Christopher B. Brooke, Jonathan W. Yewdell

PLOS Pathogens: published January 18, 2018 | https://doi.org/10.1371/journal.ppat.1006796

Xylose donor transport is critical for fungal virulence

Lucy X. Li, Carsten Rautengarten, Joshua L. Heazlewood, Tamara L. Doering

PLOS Pathogens: published January 18, 2018 | https://doi.org/10.1371/journal.ppat.1006765

Higher sequence diversity in the vaginal tract than in blood at early HIV-1 infection

Katja Klein, Gabrielle Nickel, Immaculate Nankya, Fred Kyeyune, Korey Demers, Emmanuel Ndashimye, Cynthia Kwok, Pai-Lien Chen, Sandra Rwambuya, Art Poon, Marshall Munjoma, Tsungai Chipato, Josaphat Byamugisha, Peter Mugyenyi, Robert A. Salata, Charles S. Morrison, Eric J. Arts

PLOS Pathogens: published January 18, 2018 | https://doi.org/10.1371/journal.ppat.1006754

Ebola virus requires a host scramblase for externalization of phosphatidylserine on the surface of viral particles

Asuka Nanbo, Junki Maruyama, Masaki Imai, Michiko Ujie, Yoichiro Fujioka, Shinya Nishide, Ayato Takada, Yusuke Ohba, Yoshihiro Kawaoka

PLOS Pathogens: published January 16, 2018 | https://doi.org/10.1371/journal.ppat.1006848

A novel Gerstmann-Sträussler-Scheinker disease mutation defines a precursor for amyloidogenic 8 kDa PrP fragments and reveals N-terminal structural changes shared by other GSS alleles

Robert C. C. Mercer, Nathalie Daude, Lyudmyla Dorosh, Ze-Lin Fu, Charles E. Mays, Hristina Gapeshina, Serene L. Wohlgemuth, Claudia Y. Acevedo-Morantes, Jing Yang, Neil R. Cashman, Michael B. Coulthart, Dawn M. Pearson, Jeffrey T. Joseph, Holger Wille, Jiri G. Safar, Gerard H. Jansen, Maria Stepanova, Brian D. Sykes, David Westaway

PLOS Pathogens: published January 16, 2018 | https://doi.org/10.1371/journal.ppat.1006826

STAT3 expression by myeloid cells is detrimental for the T- cell-mediated control of infection with Mycobacterium tuberculosis

Yu Gao, Juan Ignacio Basile, Cajsa Classon, Dolores Gavier-Widen, Akihiko Yoshimura, Berit Carow, Martin E. Rottenberg

PLOS Pathogens: published January 16, 2018 | https://doi.org/10.1371/journal.ppat.1006809

Effect of analytical treatment interruption and reinitiation of antiretroviral therapy on HIV reservoirs and immunologic parameters in infected individuals

Katherine E. Clarridge, Jana Blazkova, Kevin Einkauf, Mary Petrone, Eric W. Refsland, J. Shawn Justement, Victoria Shi, Erin D. Huiting, Catherine A. Seamon, Guinevere Q. Lee, Xu G. Yu, Susan Moir, Michael C. Sneller, Mathias Lichterfeld, Tae-Wook Chun

PLOS Pathogens: published January 11, 2018 | https://doi.org/10.1371/journal.ppat.1006792

Beta HPV38 oncoproteins act with a hit-and-run mechanism in ultraviolet radiation-induced skin carcinogenesis in mice

Daniele Viarisio, Karin Müller-Decker, Rosita Accardi, Alexis Robitaille, Matthias Dürst, Katrin Beer, Lars Jansen, Christa Flechtenmacher, Matthias Bozza, Richard Harbottle, Catherine Voegele, Maude Ardin, Jiri Zavadil, Sandra Caldeira, Lutz Gissmann, Massimo Tommasino

PLOS Pathogens: published January 11, 2018 | https://doi.org/10.1371/journal.ppat.1006783

Continental synchronicity of human influenza virus epidemics despite climactic variation

Jemma L. Geoghegan, Aldo F. Saavedra, Sebastián Duchêne, Sheena Sullivan, Ian Barr, Edward C. Holmes

PLOS Pathogens: published January 11, 2018 | https://doi.org/10.1371/journal.ppat.1006780

Prohibitin plays a critical role in Enterovirus 71 neuropathogenesis

Issac Horng Khit Too, Isabelle Bonne, Eng Lee Tan, Justin Jang Hann Chu, Sylvie Alonso

PLOS Pathogens: published January 11, 2018 | https://doi.org/10.1371/journal.ppat.1006778

Strains of bacterial species induce a greatly varied acute adaptive immune response: The contribution of the accessory genome

Uri Sela, Chad W. Euler, Joel Correa da Rosa, Vincent A. Fischetti

PLOS Pathogens: published January 11, 2018 | https://doi.org/10.1371/journal.ppat.1006726

The potent effect of mycolactone on lipid membranes

Milène Nitenberg, Anaïs Bénarouche, Ofelia Maniti, Estelle Marion, Laurent Marsollier, Julie Géan, Erick J. Dufourc, Jean-François Cavalier, Stéphane Canaan, Agnès P. Girard-Egrot

PLOS Pathogens: published January 10, 2018 | https://doi.org/10.1371/journal.ppat.1006814

Distinct temporal roles for the promyelocytic leukaemia (PML) protein in the sequential regulation of intracellular host immunity to HSV-1 infection

Thamir Alandijany, Ashley P. E. Roberts, Kristen L. Conn, Colin Loney, Steven McFarlane, Anne Orr, Chris Boutell

PLOS Pathogens: published January 8, 2018 | https://doi.org/10.1371/journal.ppat.1006769

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The Vibrio cholerae RND efflux systems impact virulence factor production and adaptive responses via periplasmic sensor proteins

X. Renee Bina, Mondraya F. Howard, Dawn L. Taylor-Mulneix, Vanessa M. Ante, Dillon E. Kunkle, James E. Bina

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Internal genes of a highly pathogenic H5N1 influenza virus determine high viral replication in myeloid cells and severe outcome of infection in mice

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Mycobacterium tuberculosis-induced miR-155 subverts autophagy by targeting ATG3 in human dendritic cells

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Exosomes serve as novel modes of tick-borne flavivirus transmission from arthropod to human cells and facilitates dissemination of viral RNA and proteins to the vertebrate neuronal cells

Wenshuo Zhou, Michael Woodson, Biswas Neupane, Fengwei Bai, Michael B. Sherman, Kyung H. Choi, Girish Neelakanta, Hameeda Sultana

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The paradox of HBV evolution as revealed from a 16^th century mummy

Zoe Patterson Ross, Jennifer Klunk, Gino Fornaciari, Valentina Giuffra, Sebastian Duchêne, Ana T. Duggan, Debi Poinar, Mark W. Douglas, John-Sebastian Eden, Edward C. Holmes, Hendrik N. Poinar

PLOS Pathogens: published January 4, 2018 | https://doi.org/10.1371/journal.ppat.1006750

The common HAQ STING variant impairs cGAS-dependent antibacterial responses and is associated with susceptibility to Legionnaires’ disease in humans

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Indole-3-acetaldehyde dehydrogenase-dependent auxin synthesis contributes to virulence of Pseudomonas syringae strain DC3000

Sheri A. McClerklin, Soon Goo Lee, Christopher P. Harper, Ron Nwumeh, Joseph M. Jez, Barbara N. Kunkel

PLOS Pathogens: published January 2, 2018 | https://doi.org/10.1371/journal.ppat.1006811

Memory CD8 T cells mediate severe immunopathology following respiratory syncytial virus infection

Megan E. Schmidt, Cory J. Knudson, Stacey M. Hartwig, Lecia L. Pewe, David K. Meyerholz, Ryan A. Langlois, John T. Harty, Steven M. Varga

PLOS Pathogens: published January 2, 2018 | https://doi.org/10.1371/journal.ppat.1006810

Tomato leaf curl Yunnan virus-encoded C4 induces cell division through enhancing stability of Cyclin D 1.1 via impairing NbSKη -mediated phosphorylation in Nicotiana benthamiana

Yuzhen Mei, Xiuling Yang, Changjun Huang, Xiuren Zhang, Xueping Zhou

PLOS Pathogens: published January 2, 2018 | https://doi.org/10.1371/journal.ppat.1006789

Herpes simplex viruses activate phospholipid scramblase to redistribute phosphatidylserines and Akt to the outer leaflet of the plasma membrane and promote viral entry

Natalia Cheshenko, Carl Pierce, Betsy C. Herold

PLOS Pathogens: published January 2, 2018 | https://doi.org/10.1371/journal.ppat.1006766

A role for small RNA in regulating innate immunity during plant growth

Yingtian Deng, Jubin Wang, Jeffrey Tung, Dan Liu, Yingjia Zhou, Shuang He, Yunlian Du, Barbara Baker, Feng Li

PLOS Pathogens: published January 2, 2018 | https://doi.org/10.1371/journal.ppat.1006756

Kuva HSV-1 genomista

https://www.researchgate.net/profile/Filip_Lim/publication/259626032/figure/fig1/AS:337840660598784@1457558898550/Fig-1-Genome-organization-of-Herpes-Simplex-Virus-Type-1-HSV-1-and-gene-expression.png
 +Netistä löytyy
myös hyviä videoita herpse Simplex-1 viruksen infektiosyklistä.
https://www.youtube.com/watch?v=foo0ioyG0ig
Tämäkin valiasee hyvin asiaa. Varsinkin miten tegumenmateriaali poimitaan virioniin mukaan.

Uusi teesi 2018 HSV-1 viruksesta Götgeborgin yliopistosta

Väittelija on  Zhiyuan Zhao.
Väitöstyön nimi:  Molecular aspects on herpes simplex virus  type 1 DNA replication and gene expression.  Väitöstilaisuus on vielä edessä päin 26.1. Carl Kylberg salissa ja opponentti on Uumajan  yliopistosta   professori E Johansson.
Väitöstyön  abstraktin ja osatöiden sisältöä  saa tietää  lähteestä
http://hdl.handle.net/2077/53912 
Tässä työssä tutkijat ovat  selvitelleet HSV-1 virusproteiinien keskinäistä vuorovaikutusta  viruksen  molekulaarisessa koneistossa.
 Lisäksi he ovat tutkineet niitä molekulaarisia tarpeita, mitä viruksen DNA-replikaatiosta riippuvaisten myöhäisten geenien ilmenemiseen vaaditaan.  Tarkka tieto  näistä molekyylitason  tapahtumista on avuksi kehiteltäessä antivirusterapioita ja ehkä  edistyy samalla  tietämys  omien solujemmekin vastaavista tapahtumista.

Tutkijaryhmä on osoittanut lajispesifiseksi  ne   HSV-1 viruksesta löydetyt  seitsemän proteiinia, jotka  ovat   sen DNA-replikaatiossa  välttämättömiä.  Niitä proteiineja ei voi korvata  lähisukuisen viruksen homologisella proteiinilla. Siis ne seitsemän replikaatioproteiinia muodostavat eräänlaisen molekulaarisen koneiston, replisomin ja sille on ominaista lukuisat proteiini_proteiini-interaktiot.

Lisäksi tutkijaryhmä tunnisti HSV-1-helikaasi-primaasi-kompleksista entsymaattisesti inaktiivin  UL8-proteiinin tärkeät aminohapot. Tämä  UL8 tarvitaan interaktioon  primaasikompleksin  UL52- komponentin kanssa.  Jos näissä UL8- aminohapoissa oli mutaatio,  interaktio  vaikeutui ja replisomin  DNA-replikaatiokapasiteetti  väheni tai jäi pois ei-permissiivisessä lämpötilassa.

Sitten tutkijat selvittivät  HSV-1- viruksen helikaasi-primaasikompleksin UL52- komponentin  ja muiden replikaatioproteiinien  väliset interaktiot. He havaitsivat UL52-proteiinista erilaisia domaaneja ja joka domaanilla oli eri interaktiopartneri.  UL52-N-terminaali teki  stabiilin interaktion UL5:n kanssa. Keskimmäinen domaani teki stabiilin interaktion UL8:n kanssa.  UL52-C-terminaali teki vain  ohimenevän heikon interaktion UL5:n kanssa.

Uudet  anti-HSV-1-lääkkeet   kohdentavat vaikutuksensa juuri helikaasi-primaasikompleksiin, mutta ei ole tiedetty, millä tavalla ne ovat inhibitorisia eli replikaatiota estäviä. Nyt tutkijaryhmä on osoittanut, että  nämä uudet lääkkeet estävät  HSV-1 DNA:n replikaation  vaikuttamalla UL5- ja UL52-  proteiinien väliseen interaktioon.  He ovat sitä mieltä, että lääkkeet lukitsevat nämä proteiinit tiettyyn konformaatioon estäen niitä olemasta avuksi viruksen DNA:n replikoitumisessa.

Tämän helikaasi-primaasi-kompleksi-interaktion lisäksi  UL52-proteiinin keskimmäinen domaani ilmentää  stabiilia vuorovaikutusta  UL29/ICP8- nimiseen proteiiniin, joka on  HSV-1 -viruksen ssDNA:ta sitova proteiini.
Näiden kahden proteiinin välinen  interaktio voisi antaa viitettä, miten  helikaasi-primaasikompleksi on HSV-1 genomissa  pakattuna  aktivoituun  replikaation alkukohtaan ja syntetisoi primeereitä   ICP8:lla verhotuilla ssDNA säikeillä.

Viraali  DNA-replikaatio on edellytys HSV-1 viruksen  todellisten myöhäisgeenien ilmenemiselle.   Tutkijaryhmä osoitti myös, että näiden todellsiten  myöhäisten geenien ilmenemä riippuu spesifisesti CDK9-kinaasista, joka on isäntäsolun proteiinikinaasi ja osallistuu solun transkription säätelyyn.  Jos  CDK9 estettiin, vaikuttui viruksen  myöhän mRNA:n transkriptio ja sen  kertymä  sytosoliin.   Toinenkin soluproteiini oli tarpeellinen viruksen myöhäisten geenien ilmenemiselle. Se on   transkriptiotekijä SPT5, joka on CDK9-kinaasin susbtraatti. CDK9-aktiivisuutta virus tarvitsi välttämättä  SPT5:n ja virusproteiini C27:n  väliseen interaktioon;  arvellaan sellaista vuorovaikutusta  tarvittavan  viraalin myöhäisen mRNA:n kypsymiseen ja kuljettamiseen pois  tumasta

 Tulokset viittaavat siihen, että HSV-1 -viruksen varsinaiset myöhäiset geenit ainakin osittain säätyvät  viraalin myöhäisen  mRNA:n  kypsymisestä ja tumasta poiskuljetuksesta 

I. Muylaert, I, Zhao, Z, Andersson, T, Elias P. Identification of Conserved Amino Acids in the Herpes Simplex Virus Type 1 UL8 Protein Required for DNA Synthesis and UL52 Primase Interaction in the Virus Replisome J Biol Chem. 2009 July; 287(40): 33142-52. VIEW ARTICLE II. Muylaert I, Zhao, Z, Elias P. UL52 Primase Interactions in the Herpes Simplex Virus 1 Helicase-Primase Are Affected by Antiviral Compounds and Mutations Causing Drug Resistance J Biol Chem. 2014 October; 289(47): 32583-92. VIEW ARTICLE III. Zhao, Z , Tang KW , Muylaert I, Samuelsson T, Elias P. CDK9 and SPT5 proteins are specifically required for expression of herpes simplex virus 1 replication-dependent late genes J Biol Chem. 2017 July; 292(37): 15489-00. VIEW ARTICLE

Date of Defence:

2018-01-26

HSV-1 Herpes simplex virus on aktiivin tutkimuksen kohde

PubMed  haku

Structure of the Herpes Simplex Virus 1 Genome: Manipulation of Nicks and Gaps Can Abrogate Infectivity and Alter the Cellular DNA Damage Response

Samantha Smith, Nina Reuven, Kareem N. Mohni, April J. Schumacher, Sandra K. Weller

J Virol. 2014 Sep; 88(17): 10146–10156. doi: 10.1128/JVI.01723-14

PMCID:

PMC4136335

Article PubReader PDF–1.0MCitation

Is Cited by the Following 12 Articles in this Archive:

The Non-Homologous End Joining Protein PAXX Acts to Restrict HSV-1 Infection

Ben J. Trigg, Katharina B. Lauer, Paula Fernandes dos Santos, Heather Coleman, Gabriel Balmus, Daniel S. Mansur, Brian J. Ferguson

Viruses. 2017 Nov; 9(11): 342. Published online 2017 Nov 16. doi: 10.3390/v9110342

PMCID:

PMC5707549

Article PubReader PDF–3.1MCitation

The Exonuclease Activity of Herpes Simplex Virus 1 UL12 Is Required for Production of Viral DNA That Can Be Packaged To Produce Infectious Virus

Lorry M. Grady, Renata Szczepaniak, Ryan P. Murelli, Takeshi Masaoka, Stuart F. J. Le Grice, Dennis L. Wright, Sandra K. Weller

J Virol. 2017 Dec 1; 91(23): e01380-17. Prepublished online 2017 Sep 27. Published online 2017 Nov 14. doi: 10.1128/JVI.01380-17

PMCID:

PMC5686714

Currently embargoed: Free in PMC on May 14, 2018; PubMed

The Herpesvirus Nuclear Egress Complex Component, UL31, Can Be Recruited to Sites of DNA Damage Through Poly-ADP Ribose Binding

Maxwell R. Sherry, Thomas J. M. Hay, Michael A. Gulak, Arash Nassiri, Renée L. Finnen, Bruce W. Banfield

Sci Rep. 2017; 7: 1882. Published online 2017 May 15. doi: 10.1038/s41598-017-02109-0

PMCID:

PMC5432524

Article PubReader PDF–3.6MCitation

An Intrinsically Disordered Region of the DNA repair protein Nbs1 Is a Species-Specific Barrier to Herpes Simplex Virus 1 in Primates

Dianne I. Lou, Eui Tae Kim, Nicholas R. Meyerson, Neha J. Pancholi, Kareem N. Mohni, David Enard, Dmitri A. Petrov, Sandra K. Weller, Matthew D. Weitzman, Sara L. Sawyer

Cell Host Microbe. Author manuscript; available in PMC 2017 Aug 10.

Published in final edited form as: Cell Host Microbe. 2016 Aug 10; 20(2): 178–188. doi: 10.1016/j.chom.2016.07.003

PMCID:

PMC4982468

Article PubReader PDF–1.3MCitation

Functional prediction of differentially expressed lncRNAs in HSV-1 infected human foreskin fibroblasts

Benxia Hu, Yongxia Huo, Guijun Chen, Liping Yang, Dongdong Wu, Jumin Zhou

Virol J. 2016; 13: 137. Published online 2016 Aug 5. doi: 10.1186/s12985-016-0592-5

PMCID:

PMC4974703

Article PubReader PDF–1.4MCitation

Cellular responses to HSV-1 infection are linked to specific types of alterations in the host transcriptome

Benxia Hu, Xin Li, Yongxia Huo, Yafen Yu, Qiuping Zhang, Guijun Chen, Yaping Zhang, Nigel W. Fraser, Dongdong Wu, Jumin Zhou

Sci Rep. 2016; 6: 28075. Published online 2016 Jun 29. doi: 10.1038/srep28075

PMCID:

PMC4926211

Article PubReader PDF–2.1MCitation

Topoisomerase II Inhibitors Can Enhance Baculovirus-Mediated Gene Expression in Mammalian Cells through the DNA Damage Response

Ming-Kun Liu, Jhe-Jhih Lin, Chung-Yung Chen, Szu-Cheng Kuo, Yu-Ming Wang, Hong-Lin Chan, Tzong Yuan Wu

Int J Mol Sci. 2016 Jun; 17(6): 931. Published online 2016 Jun 14. doi: 10.3390/ijms17060931

PMCID:

PMC4926464

Article PubReader PDF–5.0MCitation

ICP8 Filament Formation Is Essential for Replication Compartment Formation during Herpes Simplex Virus Infection

Anthar S. Darwish, Lorry M. Grady, Ping Bai, Sandra K. Weller

J Virol. 2016 Mar 1; 90(5): 2561–2570. Prepublished online 2015 Dec 16. Published online 2016 Feb 11. doi: 10.1128/JVI.02854-15

PMCID:

PMC4810729

Article PubReader PDF–3.4MCitation

H2AX phosphorylation and DNA damage kinase activity are dispensable for herpes simplex virus replication

Carolyn Botting, Xu Lu, Steven J. Triezenberg

Virol J. 2016; 13: 15. Published online 2016 Jan 27. doi: 10.1186/s12985-016-0470-1

PMCID:

PMC4728825

Article PubReader PDF–644KCitation

Selective Recruitment of Nuclear Factors to Productively Replicating Herpes Simplex Virus Genomes

Jill A. Dembowski, Neal A. DeLuca

PLoS Pathog. 2015 May; 11(5): e1004939. Published online 2015 May 27. doi: 10.1371/journal.ppat.1004939

PMCID:

PMC4446364

Article PubReader PDF–10MCitation

Selective recruitment of host factors by HSV-1 replication centers

Feng-Chao LANG, Xin LI, Olga VLADMIROVA, Zhuo-Ran LI, Gui-Jun CHEN, Yu XIAO, Li-Hong LI, Dan-Feng LU, Hong-Bo HAN, Ju-Min ZHOU

Dongwuxue Yanjiu. 2015 May 18; 36(3): 142–151. Published online 2015 May 18.

PMCID:

PMC4790689

Article PubReader PDF–11MCitation

HSV-I and the cellular DNA damage response

Samantha Smith, Sandra K Weller

Future Virol. Author manuscript; available in PMC 2016 Feb 1.

Published in final edited form as: Future Virol. 2015 Apr; 10(4): 383–397. doi: 10.2217/fvl.15.18

PMCID:

PMC4508672

Article PubReader PDF–655KCitation

Vuoden 2016 väitöskirja herpes-1 viruksesta

Title: Herpes Simplex Virus 1 DNA replication and its role in recombination and transcription Authors: Tang, Ka-Wei 

http://hdl.handle.net/2077/40883

I. Olsson M, Tang KW, Persson C, Wilhelmsson LM, Billeter M, Elias P. Stepwise evolution of the herpes simplex virus origin binding protein and origin of replication. J Biol Chem. 2009 Jun 12;284(24):16246-55. VIEW ARTICLE II. Tang KW, Norberg P, Holmudden M, Elias P, Liljeqvist JÅ. Rad51 and Rad52 are involved in homologous recombination of replicating herpes simplex virus DNA. PLoS One. 2014 Nov 3;9(11):e111584. VIEW ARTICLE III. Tang KW, Zhao ZY, Samuelsson T, Elias P. Replication-dependent expression of herpes simplex virus 1 late genes is controlled by P-TEFb and SIF. Manuscript

Date of Defence:

2016-01-22

Herpes simplex virus 1 (HSV-1) is one of nine different herpesvirus infecting man. They are all capable of establishing a life-long latent state following the primary infection. HSV-1 as well as other herpesviruses may reactivate from the latent state and give rise to a productive infection with clinical symptoms or asymptomatic shedding. HSV-1 infections are primarily treated by targeting the viral DNA replication carried out by a molecular machinery, a replisome, encoded by the virus.

Here we examine the mechanism of initiation of viral DNA replication and also how viral DNA replication interacts with DNA recombination and gene expression.

 In our first study we examined the initiation-step of HSV-1 replication. The origin binding protein (OBP) initiates replication by binding to the origin of replication (oriS and/or oriL). We showed, using phylogenetics and biochemical experiments, that there was a step-wise evolutionary development of herpesvirus DNA replication initiation.

The initial divergence was seen in herpesviruses acquiring an amino-acid motif RVKNL in OBP which binds the sequence TTCGCAC in the oriS. The next step was the development of an ICP8 binding motif at the C-terminus of OBP and finally the arrangement of the binding-sites for OBP in the oriS-sequence and the ability to form a stable hairpin.

 We presented molecular in vitro data to support the phylogenetic analysis and thereby defining essential motifs in OBP for protein-protein and protein-DNA interactions.

The next study was focused on genetic recombination between different HSV-1 strains. We followed the propagation of HSV-1 in cells infected with one to three genotypes of HSV-1 and calculated the number of recombination events. We found evidence for Rad51 and Rad52 involvement in recombination of the unique long and unique short gene segments of HSV-1.

 We also observed an increased recombination rate in cells with retarded ligation of Okazaki-fragments. The fidelity of recombination in virus propagated through mixed infections appears to be high since expansion or shortening of repeated sequences in the US7 gene was not detected.

 In the third study we examined the replication-coupled transcription of HSV-1 late genes, which are known to depend on DNA replication for efficient expression. Using chromatin immuno-precipitation we could determine that recruitment of RNA polymerase II to late gene promoters occur even in the absence of replication. Recruitment was dependent on ICP4, but delayed in comparison with early gene promoters. These observations suggested the involvement of transcription elongation and/or maturation in the expression of gamma genes.

 By using the drug DRB, which inhibits the kinase CDK9, a component of the positive transcription elongation factor B, and siRNA against Spt5, a transcription processivity factor, we could show a specific impairment of late gene expression, with only minimal effect on early gene expression and DNA synthesis.

We suggest that CDK9 and Spt5 are specifically recruited to replicated late genes and mediate a maturation of transcribed mRNA for nuclear exit.

 In summary, we have studied essential molecular processes in the HSV-1 life cycle and identified molecular interactions as well as mechanistic pathways, which may serve as future drug targets.