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virus cell entry

Daniel C Anacker, Heather L Aloor, Caitlin N Shepard, Gina M Lenzi, Bryan A Johnson, Baek Kim, Cary A Moody
Productive replication of human papillomaviruses (HPV) is restricted to the uppermost layers of the differentiating epithelia. How HPV ensures an adequate supply of cellular substrates for viral DNA synthesis in a differentiating environment is unclear. Here, we demonstrate that HPV31 positive cells exhibit increased dNTP pools and levels of RRM2, a component of the ribonucleotide reductase (RNR) complex, which is required for de novo synthesis of dNTPs. RRM2 depletion blocks productive replication, suggesting RRM2 provides dNTPs for viral DNA synthesis in differentiating cells...
October 17, 2016: Virology
Sutas Suttiprapa, Gabriel Rinaldi, Isheng J Tsai, Victoria H Mann, Larisa Dubrovsky, Hong-Bin Yan, Nancy Holroyd, Thomas Huckvale, Caroline Durrant, Anna V Protasio, Tatiana Pushkarsky, Sergey Iordanskiy, Matthew Berriman, Michael I Bukrinsky, Paul J Brindley
Schistosomiasis is the most important helminthic disease of humanity in terms of morbidity and mortality. Facile manipulation of schistosomes using lentiviruses would enable advances in functional genomics in these and related neglected tropical diseases pathogens including tapeworms, and including their non-dividing cells. Such approaches have hitherto been unavailable. Blood stream forms of the human blood fluke, Schistosoma mansoni, the causative agent of the hepatointestinal schistosomiasis, were infected with the human HIV-1 isolate NL4-3 pseudotyped with vesicular stomatitis virus glycoprotein...
October 2016: PLoS Pathogens
Binod Kumar, Dipanjan Dutta, Jawed Iqbal, Mairaj Ahmed Ansari, Arunava Roy, Leela Chikoti, Gina Pisano, Mohanan Valiya Veettil, Bala Chandran
Kaposi's sarcoma-associated herpesvirus (KSHV) binding to the endothelial cell surface heparan sulfate is followed by sequential interactions with α3β1, αVβ3 and αVβ5 integrins and Ephrin A2 receptor tyrosine kinase (EphA2R). These interactions activate host cell pre-existing FAK, Src, PI3-K and RhoGTPase signaling cascades, c-Cbl mediated ubiquitination of receptors, recruitment of CIB1, p130Cas and Crk adaptor molecules, and membrane bleb formation leading to lipid raft dependent macropinocytosis of KSHV into human microvascular dermal endothelial (HMVEC-d) cells...
October 2016: PLoS Pathogens
N Bishara Marzook, Timothy P Newsome
The actin cytoskeleton is a crucial part of the eukaryotic cell. Viruses depend on host cells for their replication, and, as a result, many have developed ways of manipulating the actin network to promote their spread. This chapter reviews the various ways in which viruses utilize the actin cytoskeleton at discrete steps in their life cycle, from entry into the host cell, replication, and assembly of new progeny to virus release. Various actin inhibitors that function in different ways to affect proper actin dynamics can be used to parse the role of actin at these steps...
October 19, 2016: Handbook of Experimental Pharmacology
Outi Heikkilä, Pirjo Merilahti, Marika Hakanen, Eveliina Karelehto, Jonna Alanko, Maria Sukki, Saija Kiljunen, Petri Susi
BACKGROUND: Coxsackievirus A9 (CV-A9) is a pathogenic enterovirus type within the family Picornaviridae. CV-A9 infects A549 human epithelial lung carcinoma cells by attaching to the αVβ6 integrin receptor through a highly conserved Arg-Gly-Asp (RGD) motif, which is located at the exposed carboxy-terminus of the capsid protein VP1 detected in all studied clinical isolates. However, genetically-modified CV-A9 that lacks the RGD motif (CV-A9-RGDdel) has been shown to be infectious in some cell lines but not in A549, suggesting that RGD-mediated integrin binding is not always essential for efficient entry of CV-A9...
October 18, 2016: Virology Journal
Hung-Lun Hsu, Jean K Millet, Deirdre A Costello, Gary R Whittaker, Susan Daniel
Virus pseudotyping is a useful and safe technique for studying entry of emerging strains of influenza virus. However, few studies have compared different reassortant combinations in pseudoparticle systems, or compared entry kinetics of native viruses and their pseudotyped analogs. Here, vesicular stomatitis virus (VSV)-based pseudovirions displaying distinct influenza virus envelope proteins were tested for fusion activity. We produced VSV pseudotypes containing the prototypical X-31 (H3) HA, either alone or with strain-matched or mismatched N2 NAs...
October 18, 2016: Scientific Reports
Bingjie Shi, Juan Li, Xuanling Shi, Wenxu Jia, Yi Wen, Xiongbing Hu, Fengfeng Zhuang, Jianzhong Xi, Linqi Zhang
Transcription activator-like effector nuclease (TALEN) represents a valuable tool for genomic engineering due to its single-nucleotide precision, high nuclease activity and low cytotoxicity. We report here systematic design and characterization of twenty eight novel TALENs targeting multiple regions of CCR5 gene (CCR5-TALEN) which encodes the co-receptor critical for entry of human immunodeficiency virus type I (HIV-1). By systemic characterization of these CCR5-TALENs, we have identified one (CCR5-TALEN-515) with higher nuclease activity, specificity and lower cytotoxicity compared to zinc-finger nuclease (CCR5-ZFN) currently undergoing clinical trials...
October 3, 2016: Journal of Acquired Immune Deficiency Syndromes: JAIDS
Hinojal Zazo, Clara I Colino, Klaudia T Warzecha, Mareike Hoss, Uwe Gbureck, Christian Trautwein, Frank Tacke, José M Lanao, Matthias Bartneck
The human immunodeficiency virus (HIV) continues to be a global pandemic and there is an urgent need for innovative treatment. Immune cells represent a major target of virus infection, but are also therapeutic targets. Currently, no antiretroviral therapy targets macrophages, which function as portal of entry and as major long-term deposit of HIV. It has been shown before that human macrophages efficiently internalize gold nanoparticles, a fact which might be used to target them with drug-nanoparticle conjugates...
October 17, 2016: Macromolecular Bioscience
Yu-Ming Wang, Jeng-Wei Lu, Chang-Chi Lin, Yuan-Fan Chin, Tzong-Yuan Wu, Liang-In Lin, Zheng-Zong Lai, Szu-Cheng Kuo, Yi-Jung Ho
Chikungunya disease results from an infection with the arbovirus, chikungunya virus (CHIKV). Symptoms of CHIKV include fever and persistent, severe arthritis. In recent years, several antiviral drugs have been evaluated in clinical trials; however, no registered antivirals have been approved for clinical therapy. In this study, we established a high-throughput screening (HTS) system based on CHIKV 26S mediated insect cell fusion inhibition assay. Our screening system was able to search potential anti-CHIKV drugs in vitro...
October 11, 2016: Antiviral Research
T N Figueira, L M Palermo, A S Veiga, D Huey, C A Alabi, N C Santos, J C Welsch, C Mathieu, B Horvat, S Niewiesk, A Moscona, M A R B Castanho, M Porotto
: Measles virus (MV) infection is undergoing resurgence and remains one of the leading causes of death among young children worldwide despite the availability of an effective measles vaccine. MV infects its target cells by coordinated action of the MV hemagglutinin (H) and fusion (F) envelope glycoproteins; upon receptor engagement by H, the pre-fusion F undergoes a structural transition, extending and inserting into the target cell membrane and then re-folding into a post-fusion structure that fuses the viral and cell membranes...
October 12, 2016: Journal of Virology
Kazuya Shirato, Kazuhiko Kanou, Miyuki Kawase, Shutoku Matsuyama
: Human coronavirus 229E (HCoV-229E), a causative agent of the common cold, enters host cells via two distinct pathways: one is mediated by cell surface proteases, particularly transmembrane protease serine 2 (TMPRSS2), and the other by endosomal cathepsin L. Thus, specific inhibitors of these proteases block virus infection. However, it is unclear which of these pathways is actually utilized by HCoV-229E in the human respiratory tract. Here, we examined the mechanism of cell entry used by a pseudotyped virus bearing the HCoV-229E spike (S) protein in the presence/absence of protease inhibitors...
October 12, 2016: Journal of Virology
Eric R Weiss, Galit Alter, Javier Gordon Ogembo, Jennifer L Henderson, Barbara Tabak, Yasin Bakiş, Mohan Somasundaran, Manuel Garber, Liisa Selin, Katherine Luzuriaga
: The Epstein Barr virus (EBV) gp350 glycoprotein interacts with the cellular receptor to mediate viral entry and is thought to be the major target for neutralizing antibodies. To better understand the role of EBV-specific antibodies in the control of viral replication and evolution of sequence diversity, we measured EBV gp350-specific antibody responses and sequenced the gp350 gene in samples obtained from individuals experiencing primary EBV infection (acute infectious mononucleosis; AIM) and again 6 months later (convalescence, CONV)...
October 12, 2016: Journal of Virology
Anthony Ndirangu Kamau, Jung-Eun Park, Eui-Soon Park, Jung-Eun Yu, Jae-Rang Rho, Hyun-Jin Shin
: Porcine epidemic diarrhea virus (PEDV) infects swine intestinal cells causing enteric disease. Research has shown that the entry into these cells is through porcine aminopeptidase N (pAPN) receptor. To gain insights into mechanisms of PEDV-pAPN interactions, the present study aimed at identifying the domain that is critical for PEDV binding. To this end, NIH3T3 cell lines constitutively expressing pAPN or pAPN mutants were generated. The mutants were; domain VII deletion mutant and domains IV-VI deletion mutant...
October 9, 2016: Virus Research
Bibek Parajuli, Kriti Acharya, Reina Yu, Brendon Ngo, Adel A Rashad, Cameron F Abrams, Irwin M Chaiken
We recently reported discovery of a recombinant chimera, denoted DAVEI (Dual Acting Virucidal Entry Inhibitor), which is able to selectively cause specific and potent lytic inactivation of both pseudotyped and fully infectious HIV-1 virions. The chimera is composed of the lectin cyanovirin-N (CVN) fused to the 20-residue membrane-proximal external region (MPER) of HIV-1 gp41. Since the Env gp120-binding CVN domain on its own is not lytic, we sought here to determine how the MPER(DAVEI) domain is able to endow the chimera with virolytic activity...
October 12, 2016: Biochemistry
Candela R González, Mariano Ar Amer, Alfredo D Vitullo, Silvia I González-Calvar, María I Vacas
Saliva is the first barrier to entry of bacteria and viruses into the body. The submandibular glands (SMG) contribute to the maintenance of oral health and regulation of immune/ inflam matory responses. Previous studies suggest that transforming growth factor beta 1 (TGFB1) may contribute to salivary gland fibrosis but the expression of the TGFB1 system in the SMG has not been elucidated. Thus, the aim of this study was to analyze in rat SMG the immunolocalization of TGFB1 and its specific receptors ALK5 (profibrotic) and ALK1 (proproliferative) and the coreceptor endoglin (EDG) in a bilateral experimental periodontitis (EP) model (cotton thread ligature around the neck of the first lower molars) for 1 and 6 weeks...
September 2016: Acta Odontológica Latinoamericana: AOL
Xia Wang, Sanyi Tang, Xinyu Song, Libin Rong
HIV can infect cells via virus-to-cell infection or cell-to-cell viral transmission. These two infection modes may occur in a synergistic way and facilitate viral spread within an infected individual. In this paper, we developed an HIV latent infection model including both modes of transmission and time delays between viral entry and integration or viral production. We analysed the model by defining the basic reproductive number, showing the existence, positivity and boundedness of the solution, and proving the local and global stability of the infection-free and infected steady states...
October 12, 2016: Journal of Biological Dynamics
Chang Liu, Yuanmei Ma, Yang Yang, Yuan Zheng, Jian Shang, Yusen Zhou, Shibo Jiang, Lanying Du, Jianrong Li, Fang Li
Porcine epidemic diarrhea coronavirus (PEDV) is currently devastating the US pork industry by causing 80-100% fatality rate in infected piglets. Coronavirus spike proteins mediate virus entry into cells, a process that requires the spike proteins to be proteolytically activated. It has been a conundrum what proteases activate PEDV entry. Here we systematically investigated the roles of different proteases in PEDV entry using pseudovirus entry, biochemical, and live virus infection assays. We found that PEDV spike is activated by lysosomal cysteine proteases, but not proprotein convertases or cell-surface serine proteases...
October 11, 2016: Journal of Biological Chemistry
Qian Chen, Taiyun Wei
Insect-borne propagative plant viruses of agricultural importance are transmitted by sap-sucking insects. Although the infection routes of these viruses within the bodies of insect vectors are well established, cellular receptors on the microvilli, intercellular junctions, and basal lamina for mediating viral entry or spread in insect gut epithelium have not been well identified or characterized. Recent trends in the field are opening questions on how viruses exploit actin-based tubule motility to overcome insect gut epithelium barriers after viral entry in epithelium...
August 2016: Current Opinion in Insect Science
R J G Hulswit, C A M de Haan, B-J Bosch
Coronaviruses (CoVs) have a remarkable potential to change tropism. This is particularly illustrated over the last 15 years by the emergence of two zoonotic CoVs, the severe acute respiratory syndrome (SARS)- and Middle East respiratory syndrome (MERS)-CoV. Due to their inherent genetic variability, it is inevitable that new cross-species transmission events of these enveloped, positive-stranded RNA viruses will occur. Research into these medical and veterinary important pathogens-sparked by the SARS and MERS outbreaks-revealed important principles of inter- and intraspecies tropism changes...
2016: Advances in Virus Research
B W Neuman, M J Buchmeier
Coronavirus particles serve three fundamentally important functions in infection. The virion provides the means to deliver the viral genome across the plasma membrane of a host cell. The virion is also a means of escape for newly synthesized genomes. Lastly, the virion is a durable vessel that protects the genome on its journey between cells. This review summarizes the available X-ray crystallography, NMR, and cryoelectron microscopy structural data for coronavirus structural proteins, and looks at the role of each of the major structural proteins in virus entry and assembly...
2016: Advances in Virus Research
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