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Viral trafficking

Jacob D Estes, Roger LeGrand, Constantinos Petrovas
Immunological inductive tissues, such as secondary lymphoid organs, are composed of distinct anatomical microenvironments for the generation of immune responses to pathogens and immunogens. These microenvironments are characterized by the compartmentalization of highly specialized immune and stromal cell populations, as well as the presence of a complex network of soluble factors and chemokines that direct the intra-tissue trafficking of naïve and effector cell populations. Imaging platforms have provided critical contextual information regarding the molecular and cellular interactions that orchestrate the spatial microanatomy of relevant cells and the development of immune responses against pathogens...
2018: Frontiers in Immunology
Sohail Raza, Gualtiero Alvisi, Farzana Shahin, Urooj Husain, Masood Rabbani, Tahir Yaqub, Aftab Ahmad Anjum, Ali Ahmad Sheikh, Muhammad Nawaz, Muhammad Asad Ali
Most enveloped viruses exploit complex cellular pathways for assembly and egress from the host cell, and the large DNA virus Herpes simplex virus 1 (HSV-1) makes no exception, hijacking several cellular transport pathways for its glycoprotein trafficking and maturation, as well as for viral morphogenesis and egress according to the envelopment, de-envelopment and re-envelopment model. Importantly Rab GTPases, widely distributed master regulators of intracellular membrane trafficking pathways, have recently being tightly implicated in such process...
March 15, 2018: Microbial Pathogenesis
Fei Xiao, Stanley Wang, Rina Barouch-Bentov, Gregory Neveu, Szuyuan Pu, Melanie Beer, Stanford Schor, Sathish Kumar, Vlad Nicolaescu, Brett D Lindenbach, Glenn Randall, Shirit Einav
Hepatitis C virus (HCV) spreads via secreted cell-free particles or direct cell-to-cell transmission. Yet, virus-host determinants governing differential intracellular trafficking of cell-free- and cell-to-cell-transmitted virus remain unknown. The host adaptor proteins (APs) AP-1A, AP-1B, and AP-4 traffic in post-Golgi compartments, and the latter two are implicated in basolateral sorting. We reported that AP-1A mediates HCV trafficking during release, whereas the endocytic adaptor AP-2 mediates entry and assembly...
March 13, 2018: MBio
Jon Gil-Ranedo, Eva Hernando, Noelia Valle, Laura Riolobos, Beatriz Maroto, José M Almendral
The T1 parvovirus Minute Virus of Mice (MVM) was used to study the roles that phosphorylation and N-terminal domains (Nt) configuration of capsid subunits may play in icosahedral nuclear viruses assembly. In synchronous MVM infection, capsid subunits newly assembled as two types of cytoplasmic trimeric intermediates (3VP2, and 1VP1:2VP2) harbored a VP1 phosphorylation level fivefold higher than that of VP2, and hidden Nt. Upon nuclear translocation at S phase, VP1-Nt became exposed in the heterotrimer and subsequent subviral assembly intermediates...
March 7, 2018: Virology
Jing Shi, Ran Xiong, Tao Zhou, Peiyi Su, Xihe Zhang, Xusheng Qiu, Hongmei Li, Sunan Li, Changqing Yu, Bin Wang, Chan Ding, Thomas E Smithgall, Yong-Hui Zheng
The primate lentiviral accessory protein Nef downregulates CD4 and MHC-I from the cell surface via independent endosomal trafficking pathways to promote viral pathogenesis. In addition, Nef antagonizes a novel restriction factor, SERINC5 (Ser5), to increase viral infectivity. To explore the molecular mechanism of Ser5 antagonism by Nef, we determined how Nef affects Ser5 expression and intracellular trafficking in comparison with CD4 and MHC-I. We confirm that Nef excludes Ser5 from HIV-1 virions by downregulating its cell surface expression via similar functional motifs required for CD4-downregulation...
March 7, 2018: Journal of Virology
Daniela Ponce-Balbuena, Guadalupe Guerrero-Serna, Carmen R Valdivia, Ricardo Caballero, F J Díez-Guerra, Eric N Jiménez-Vázquez, Rafael J Ramirez, Andre Monteiro da Rocha, Todd J Herron, Katherine F Campbell, B C Willis, Francisco J Alvarado, Manuel Zarzoso, Kuljeet Kaur, Marta Pérez-Hernández, Marcos Matamoros, Héctor H Valdivia, Eva Delpón, José Jalife
<u>Rationale:</u> In cardiomyocytes, NaV 1.5 and Kir2.1 channels interact dynamically as part of membrane bound macromolecular complexes. <u>Objective:</u> To test whether NaV 1.5 and Kir2.1 preassemble during early forward trafficking and travel together to common membrane microdomains. <u>Methods and Results:</u> In patch-clamp experiments, co-expression of trafficking deficient mutants Kir2.1Δ314-315 or Kir2.1R44A/R46A with wildtype (WT) NaV 1.5WT in heterologous cells reduced INa , compared to NaV 1...
March 7, 2018: Circulation Research
Melanie Laura Duncan, Jacquelyn Horsington, Preethi Eldi, Zahrah Al Rumaih, Gunasegaran Karupiah, Timothy P Newsome
Ectromelia virus (ECTV) is an orthopoxvirus and the causative agent of mousepox. Like other poxviruses such as variola virus (agent of smallpox), monkeypox virus and vaccinia virus (the live vaccine for smallpox), ECTV promotes actin-nucleation at the surface of infected cells during virus release. Homologs of the viral protein A36 mediate this function through phosphorylation of one or two tyrosine residues that ultimately recruit the cellular Arp2/3 actin-nucleating complex. A36 also functions in the intracellular trafficking of virus mediated by kinesin-1...
March 5, 2018: Viruses
Ludmila Karen Dos Santos Silva, Ana Cláudia Dos Santos Pereira Andrade, Fábio Pio Dornas, Rodrigo Araújo Lima Rodrigues, Thalita Arantes, Erna Geessien Kroon, Cláudio Antônio Bonjardim, Jônatas Santos Abrahão
The giant viruses are the largest and most complex viruses in the virosphere. In the last decade, new members have constantly been added to this group. Here, we provide an in-depth descriptive analysis of the replication cycle of Cedratvirus getuliensis, one of the largest viruses known to date. We tracked the virion entry, the early steps of virus factory and particles morphogenesis, and during this phase, we observed a complex and unique sequential organization of immature particle elements, including horseshoe and rectangular compartments, revealed by transverse and longitudinal sections, respectively, until the formation of the final ovoid-shaped striped virion...
March 5, 2018: Scientific Reports
Helen R Fryer, Steven M Wolinsky, Angela R McLean
Although antiretroviral drug therapy suppresses human immunodeficiency virus-type 1 (HIV-1) to undetectable levels in the blood of treated individuals, reservoirs of replication competent HIV-1 endure. Upon cessation of antiretroviral therapy, the reservoir usually allows outgrowth of virus and approaches to targeting the reservoir have had limited success. Ongoing cycles of viral replication in regions with low drug penetration contribute to this persistence. Here, we use a mathematical model to illustrate a new approach to eliminating the part of the reservoir attributable to persistent replication in drug sanctuaries...
March 2, 2018: PLoS Computational Biology
Jo-Ann Chuah, Keiji Numata
For efficient gene delivery in plant systems, nonviral vector and DNA complexes require extracellular stability, cell wall/membrane translocation capability, and the ability to mediate both endosomal escape and intracellular DNA release. Peptides make appealing gene delivery vectors due to their DNA-binding, cell-penetrating, and endosome escape properties. However, DNA release within cells has so far been inefficient, which results in poor and delayed gene expression, while the lack of understanding of both internalization and trafficking mechanisms is a further obstacle to the design of efficient peptide gene delivery vectors...
March 8, 2018: Biomacromolecules
Bizhan Malaekeh-Nikouei, Leila Gholami, Fariba Asghari, Saeedeh Askarian, Saeedeh Barzegar, Mehdi Rezaee, Reza Kazemi Oskuee
Non-viral vectors such as polymers and liposomes have been used as gene delivery systems to overcome intrinsic problems of viral vectors, but transfection efficiency of these vectors is lower than viral vectors. In the present study, we tried to design non-viral gene delivery vectors that mimic the viral vectors using the benefits of both cationic liposomes and cationic polymer vectors along with targeting glucocorticoid receptors to enhance cellular trafficking of vectors. Cationic liposomes containing DOTAP and cholesterol were prepared by thin-film hydration following extrusion method...
February 21, 2018: Colloids and Surfaces. B, Biointerfaces
Ritsuko Koga, Marie Kubota, Takao Hashiguchi, Yusuke Yanagi, Shinji Ohno
Annexins are a family of structurally related proteins that bind negatively charged membrane phospholipids in a Ca2+ -dependent manner. Annexin A2 (AnxA2), a member of the family, has been implicated in a variety of cellular functions including the organization of membrane domains, vesicular trafficking and cell-cell adhesion. AnxA2 generally forms the heterotetrameric complex with a small Ca2+ -binding protein S100A10. Measles virus (MV), a member of the family Paramyxoviridae , is an enveloped virus with a nonsegmented negative strand RNA genome...
February 28, 2018: Journal of Virology
Laura Riva, Ok-Ryul Song, Jannick Prentoe, François Helle, Laurent L'homme, Charles-Henry Gattolliat, Alexandre Vandeputte, Lucie Fénéant, Sandrine Belouzard, Thomas F Baumert, Tarik Asselah, Jens Bukh, Priscille Brodin, Laurence Cocquerel, Yves Rouillé, Jean Dubuisson
Hepatitis C virus (HCV) infection causes 500,000 deaths annually, associated with end-stage liver diseases. Investigations of the HCV life cycle widened the knowledge in virology, and here we discovered that two piperazinylbenzenesulfonamides inhibit HCV entry into liver cells. The entry process of HCV into host cells is a complex process, not fully understood, but characterized by multiple spatially and temporally regulated steps involving several known host factors. Through a high-content virus-infection screening analysis with a library of 1,120 biologically active chemical compounds, we identified SB258585, an antagonist of the serotonin receptor 6 (5-HT6), as a new inhibitor of HCV entry in liver-derived cell lines, as well as in primary hepatocytes...
February 28, 2018: Journal of Virology
Erik V Munsell, Deepa S Kurpad, Theresa A Freeman, Millicent O Sullivan
Skeletal tissue regeneration following traumatic injury involves a complex cascade of growth factor signals that direct the differentiation of mesenchymal stem cells (MSCs) within the fracture. The necessity for controlled and localized expression of these factors has highlighted the role gene therapy may play as a promising treatment option for bone repair. However, the design of nanocarrier systems that negotiate efficient intracellular trafficking and nuclear delivery represents a significant challenge. Recent investigations have highlighted the roles histone tail sequences play in directing nuclear delivery and activating DNA transcription...
February 23, 2018: Acta Biomaterialia
Yared Hailemichael, Amber Woods, Tihui Fu, Qiuming He, Michael C Nielsen, Farah Hasan, Jason Roszik, Zhilan Xiao, Christina Vianden, Hiep Khong, Manisha Singh, Meenu Sharma, Faisal Faak, Derek Moore, Zhimin Dai, Scott M Anthony, Kimberly S Schluns, Padmanee Sharma, Victor H Engelhard, Willem W Overwijk
Anticancer vaccination is a promising approach to increase the efficacy of cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and programmed death ligand 1 (PD-L1) checkpoint blockade therapies. However, the landmark FDA registration trial for anti-CTLA-4 therapy (ipilimumab) revealed a complete lack of benefit of adding vaccination with gp100 peptide formulated in incomplete Freund's adjuvant (IFA). Here, using a mouse model of melanoma, we found that gp100 vaccination induced gp100-specific effector T cells (Teffs), which dominantly forced trafficking of anti-CTLA-4-induced, non-gp100-specific Teffs away from the tumor, reducing tumor control...
February 26, 2018: Journal of Clinical Investigation
Svetlana Y Folimonova, Jens Tilsner
The phloem is of central importance to plant viruses, providing the route by which they spread throughout their host. Compared with virus movement in non-vascular tissue, phloem entry, exit, and long-distance translocation usually involve additional viral factors and complex virus-host interactions, probably, because the phloem has evolved additional protection against these molecular 'hitchhikers'. Recent progress in understanding phloem trafficking of endogenous mRNAs along with observations of membranous viral replication 'factories' in sieve elements challenge existing conceptions of virus long-distance transport...
February 21, 2018: Current Opinion in Plant Biology
Cyprien Beraud, Morgane Lemaire, Danielle Perez Bercoff
The cytoplasmic domain of lentiviral Envelopes (EnvCD) ensures Env incorporation into nascent virions and regulates Env trafficking to and from the plasma membrane. It has also been reported to promote transcription from the viral LTR both directly and indirectly. Noticeably, the HIV-1 and SIVmac239 EnvCDs were described to trigger nuclear translocation of NF-κB (Postler, Cell Host Microbes 2012). Given the paramount importance of identifying viral and host factors regulating HIV transcription, cellular signaling pathways and latency, and given that viral replication capacity is dependent on Env, we asked whether HIV EnvCDs from different HIV-1 subtypes differently modulated NF-κB...
February 17, 2018: Virology Journal
Fabio Zanini, Szu-Yuan Pu, Elena Bekerman, Shirit Einav, Stephen R Quake
Dengue and Zika viral infections affect millions of people annually and can be complicated by hemorrhage or neurological manifestations, respectively. However, a thorough understanding of the host response to these viruses is lacking, partly because conventional approaches ignore heterogeneity in virus abundance across cells. We present viscRNA-Seq (virus-inclusive single cell RNA-Seq), an approach to probe the host transcriptome together with intracellular viral RNA at the single cell level. We applied viscRNA-Seq to monitor dengue and Zika virus infection in cultured cells and discovered extreme heterogeneity in virus abundance...
February 16, 2018: ELife
Liping Yang, Rong Wang, Shixing Yang, Zexu Ma, Shaoli Lin, Yuchen Nan, Qisheng Li, Qiyi Tang, Yan-Jin Zhang
Movement of macromolecules between the cytoplasm and the nucleus occurs through the nuclear pore complex (NPC). Karyopherins comprise a family of soluble transport factors facilitating nucleocytoplasmic translocation of proteins through the NPC. In this study, we discovered that karyopherin alpha6 (KPNA6, also known as importin alpha7) was required for the optimal replication of porcine reproductive and respiratory syndrome virus (PRRSV) and Zika virus (ZIKV), which are positive-sense, single-stranded RNA viruses replicating in the cytoplasm...
February 14, 2018: Journal of Virology
Ga Ram Jeong, Eun-Hae Jang, Jae Ryul Bae, Soyoung Jun, Ho Chul Kang, Chi-Hu Park, Joo-Ho Shin, Yukio Yamamoto, Keiko Tanaka-Yamamoto, Valina L Dawson, Ted M Dawson, Eun-Mi Hur, Byoung Dae Lee
BACKGROUND: Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of familial and sporadic Parkinson's disease (PD). Elevated kinase activity is associated with LRRK2 toxicity, but the substrates that mediate neurodegeneration remain poorly defined. Given the increasing evidence suggesting a role of LRRK2 in membrane and vesicle trafficking, here we systemically screened Rab GTPases, core regulators of vesicular dynamics, as potential substrates of LRRK2 and investigated the functional consequence of such phosphorylation in cells and in vivo...
February 13, 2018: Molecular Neurodegeneration
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