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Růžena Píchalová, Tibor Füzik, Barbora Vokatá, Michaela Rumlová, Manuel Llano, Alžběta Dostálková, Ivana Křížová, Tomáš Ruml, Pavel Ulbrich
Retrovirus assembly is driven mostly by Gag polyprotein oligomerization, which is mediated by inter and intra protein-protein interactions among its capsid (CA) domains. Mason-Pfizer monkey virus (M-PMV) CA contains three cysteines (C82, C193 and C213), where the latter two are highly conserved among most retroviruses. To determine the importance of these cysteines, we introduced mutations of these residues in both bacterial and proviral vectors and studied their impact on the M-PMV life cycle. These studies revealed that the presence of both conserved cysteines of M-PMV CA is necessary for both proper assembly and virus infectivity...
June 12, 2018: Virology
Xiaoyu Xu, Huayao Zhao, Zhen Gong, Guan-Zhu Han
The deep history and early diversification of retroviruses remains elusive, largely because few retroviruses have been characterized in vertebrates other than mammals and birds. Endogenous retroviruses (ERVs) documented past retroviral infections and thus provide 'molecular fossils' for studying the deep history of retroviruses. Here we perform a comprehensive phylogenomic analysis of ERVs within the genomes of 92 non-avian/mammalian vertebrates, including 72 fishes, 4 amphibians, and 16 reptiles. We find that ERVs are present in all the genomes of jawed vertebrates, revealing the ubiquitous presence of ERVs in jawed vertebrates...
June 2018: PLoS Pathogens
Duane P Grandgenett, Hideki Aihara
Integration of the reverse-transcribed viral cDNA into the host's genome is a critical step in the lifecycle of all retroviruses. Retrovirus integration is carried out by integrase (IN), a virus-encoded enzyme that forms an oligomeric 'intasome' complex with both ends of the linear viral DNA to catalyze their concerted insertions into the backbones of the host's DNA. IN also forms a complex with host proteins, which guides the intasome to the host's chromosome. Recent structural studies have revealed remarkable diversity as well as conserved features among the architectures of the intasome assembly from different genera of retroviruses...
2018: Sub-cellular Biochemistry
Robert Craigie
Integration of a DNA copy of the viral genome into host DNA is an essential step in the replication cycle of HIV-1 and other retroviruses and is an important therapeutic target for drugs. DNA integration is catalyzed by the viral integrase protein and proceeds through a series of stable nucleoprotein complexes of integrase, viral DNA ends and target DNA. These nucleoprotein complexes are collectively called intasomes. Retroviral intasomes undergo a series of transitions between initial formation and catalysis of the DNA cutting and joining steps of DNA integration...
2018: Sub-cellular Biochemistry
Wei Zhang, Luiza Mendonça, Louis L Mansky
The retrovirus capsid core is a metastable structure that disassembles during the early phase of viral infection after membrane fusion. The core is intact and permeable to essential nucleotides during reverse transcription, but it undergoes disassembly for nuclear entry and genome integration. Increasing or decreasing the stability of the capsid core has a substantial negative impact on virus infectivity, which makes the core an attractive anti-viral target. The retrovirus capsid core also encounters a variety of virus- and organism-specific host cellular factors that promote or restrict viral replication...
2018: Sub-cellular Biochemistry
Diego Ferrero, Cristina Ferrer-Orta, Núria Verdaguer
Most emerging and re-emerging human and animal viral diseases are associated with RNA viruses. All these pathogens, with the exception of retroviruses, encode a specialized enzyme called RNA-dependent RNA polymerase (RdRP), which catalyze phosphodiester-bond formation between ribonucleotides (NTPs) in an RNA template-dependent manner. These enzymes function either as single polypeptides or in complex with other viral or host components to transcribe and replicate the viral RNA genome. The structures of RdRPs and RdRP catalytic complexes, currently available for several members of (+) ssRNA, (-)ssRNA and dsRNA virus families, have provided high resolution snapshots of the functional steps underlying replication and transcription of viral RNA genomes and their regulatory mechanisms...
2018: Sub-cellular Biochemistry
Dudi Shneor, Shay Tayeb, Jacob Pe'er, Hanna Voropaev, Maria Gimmelshein, Nathalie Cassoux, Alik Honigman, Shahar Frenkel
Uveal melanoma (UM) is the most frequent intraocular tumor in adult patients. When metastases occur, systemic therapy with alkylating agents (fotemustine or dacarbazine (DTIC)) has shown only modest efficacy. The common chemotherapeutic drug doxorubicin (DOX) is not used to treat metastatic UM (mUM). To expand the chemotherapeutic arsenal for mUM, we tested the effect of DOX on UM cell mortality. We have previously shown that CREB knockdown enhances sensitivity to DOX. UM cells infected with recombinant MuLV-based replicative competent retroviruses (RCR) expressing shRNA targeting CREB were co-treated with either DTIC or DOX...
May 25, 2018: Oncotarget
Alice G Russo, John-Sebastian Eden, Daniel Enosi Tuipulotu, Mang Shi, Daniel Selechnik, Richard Shine, Lee Ann Rollins, Edward C Holmes, Peter A White
Cane toads are a notorious invasive species, inhabiting over 1.2 million km2 of Australia and threatening native biodiversity. Release of pathogenic cane toad viruses is one possible biocontrol strategy yet is currently hindered by the poorly-described cane toad virome. Metatranscriptomic analysis of 16 cane toad livers revealed the presence of a novel and full-length picornavirus, Rhimavirus A (RhiV-A), a member of a reptile and amphibian specific-cluster of the Picornaviridae basal to the Kobuvirus -like group...
June 13, 2018: Journal of Virology
Eiichi Shoguchi, Girish Beedessee, Ipputa Tada, Kanako Hisata, Takeshi Kawashima, Takeshi Takeuchi, Nana Arakaki, Manabu Fujie, Ryo Koyanagi, Michael C Roy, Masanobu Kawachi, Michio Hidaka, Noriyuki Satoh, Chuya Shinzato
BACKGROUND: The marine dinoflagellate, Symbiodinium, is a well-known photosynthetic partner for coral and other diverse, non-photosynthetic hosts in subtropical and tropical shallows, where it comprises an essential component of marine ecosystems. Using molecular phylogenetics, the genus Symbiodinium has been classified into nine major clades, A-I, and one of the reported differences among phenotypes is their capacity to synthesize mycosporine-like amino acids (MAAs), which absorb UV radiation...
June 14, 2018: BMC Genomics
Masaki Ikeda, Kazuhiro Satomura, Tsuyoshi Sekizuka, Kentaro Hanada, Toshinori Endo, Naoki Osada
Simian retrovirus (SRV) is a type-D betaretrovirus infectious to the Old World monkeys causing a variety of symptoms. SRVs are also present in the Old World monkey genomes as endogenous forms, which are referred to as Simian endogenous retroviruses (SERVs). Although many SERV sequences have been identified in Cercopithecinae genomes, with potential of encoding all functional genes, the distribution of SERVs in genomes and evolutionary relationship between exogeneous SRVs and SERVs remains unclear. In this study, we comprehensively investigated seven draft genome sequences of the Old World monkeys, and identified a novel cluster of SERVs in the two Rhinopithecus (R...
June 12, 2018: American Journal of Primatology
Bonnie L Quigley, Scott Carver, Jon Hanger, Miranda E Vidgen, Peter Timms
Chlamydia is a major bacterial pathogen in humans and animals globally. Yet 80% of infections never progress to clinical disease. Decades of research have generated an interconnected network linking pathogen, host, and environmental factors to disease expression, but the relative importance of these and whether they account for disease progression remains unknown. To address this, we used structural equation modeling to evaluate putative factors likely to contribute to urogenital and ocular chlamydial disease in the koala (Phascolarctos cinereus)...
June 11, 2018: Scientific Reports
Yantao Yang, Na Qu, Jie Tan, Muaz N Rushdi, Christopher J Krueger, Antony K Chen
During HIV-1 assembly, the retroviral structural protein Gag forms an immature capsid, containing thousands of Gag molecules, at the plasma membrane (PM). Interactions between Gag nucleocapsid (NC) and viral RNA (vRNA) are thought to drive assembly, but the exact roles of these interactions have remained poorly understood. Since previous studies have shown that Gag dimer- or trimer-forming mutants (GagZiL ) lacking an NC domain can form immature capsids independent of RNA binding, it is often hypothesized that vRNA drives Gag assembly by inducing Gag to form low-ordered multimers, but is dispensable for subsequent assembly...
June 11, 2018: Proceedings of the National Academy of Sciences of the United States of America
Wencheng Lin, Zhouyi Xu, Yiming Yan, Huanmin Zhang, Hongxin Li, Weiguo Chen, Feng Chen, Qingmei Xie
Avian leukosis virus subgroup J (ALV-J) is an oncogenic retrovirus that causes immunosuppression and enhances susceptibility to secondary infection, resulting in great economic losses. Although ALV-J-induced immunosuppression has been well established, the underlying molecular mechanism for such induction is still unclear. Here, we report that the inhibitory effect of ALV-J infection on type I interferon expression is associated with the down-regulation of transcriptional regulator NF-κB in host cells. We found that ALV-J possess the inhibitory effect on type I interferon production in HD11 cells and that ALV-J causes the up-regulation of IκBα and down-regulation of NF-κB p65, and that ALV-J blocks the phosphorylation of IκBα on Ser32/36 amino acid residues...
2018: Frontiers in Microbiology
Bjørn A Nexø
Recent genetic evidence points towards endogenous retroviruses as playing a pivotal role in the causation of multiple sclerosis and possibly other autoimmune diseases. We discuss various ways in which this association could be brought about. Specifically, we suggest that two endogenous retroviruses, HERV-Fc1 and HERV-K13, on chromosomes X and 19, respectively, contribute to the development of autoimmune T cells by transforming them in multiple sclerosis. Partially overlapping sets of endogenous retroviruses may play a role in other autoimmune diseases...
June 8, 2018: Immunologic Research
Caiwei Guo, Hyun-Hwan Jeong, Yi-Chen Hsieh, Hans-Ulrich Klein, David A Bennett, Philip L De Jager, Zhandong Liu, Joshua M Shulman
Aging and neurodegenerative disease are characterized by genomic instability in neurons, including aberrant activation and mobilization of transposable elements (TEs). Integrating studies of human postmortem brain tissue and Drosophila melanogaster models, we investigate TE activation in association with Tau pathology in Alzheimer's disease (AD). Leveraging RNA sequencing from 636 human brains, we discover differential expression for several retrotransposons in association with neurofibrillary tangle burden and highlight evidence for global TE transcriptional activation among the long interspersed nuclear element 1 and endogenous retrovirus clades...
June 5, 2018: Cell Reports
Alfredo Fusco, Giuseppe Portella, Pier Paolo Di Fiore, Maria Teresa Berlingieri, Roberto Di Lauro, Arthur B Schneider, Giancarlo Vecchio
[This retracts the article DOI: 10.1128/JVI.56.1.284-292.1985.].
March 15, 2018: Journal of Virology
Alisa A Garaeva, Gert T Oostergetel, Cornelius Gati, Albert Guskov, Cristina Paulino, Dirk J Slotboom
Human ASCT2 belongs to the SLC1 family of secondary transporters and is specific for the transport of small neutral amino acids. ASCT2 is upregulated in cancer cells and serves as the receptor for many retroviruses; hence, it has importance as a potential drug target. Here we used single-particle cryo-EM to determine a structure of the functional and unmodified human ASCT2 at 3.85-Å resolution. ASCT2 forms a homotrimeric complex in which each subunit contains a transport and a scaffold domain. Prominent extracellular extensions on the scaffold domain form the predicted docking site for retroviruses...
June 2018: Nature Structural & Molecular Biology
Spyridon Stavrou, Alexya N Aguilera, Kristin Blouch, Susan R Ross
Host recognition of viral nucleic acids generated during infection leads to the activation of innate immune responses essential for early control of virus. Retrovirus reverse transcription creates numerous potential ligands for cytosolic host sensors that recognize foreign nucleic acids, including single-stranded RNA (ssRNA), RNA/DNA hybrids, and double-stranded DNA (dsDNA). We and others recently showed that the sensors cyclic GMP-AMP synthase (cGAS), DEAD-box helicase 41 (DDX41), and members of the Aim2-like receptor (ALR) family participate in the recognition of retroviral reverse transcripts...
June 5, 2018: MBio
Juraj Sokol, Maria Skerenova, Jela Ivankova, Tomas Simurda, Jan Stasko
The aim of this study was to evaluate the genetic variability of the selected single nucleotide polymorphisms (SNPs) and examine the association between these SNPs and risk for deep vein thrombosis (DVT) in patients with sticky platelet syndrome (SPS). We examined 84 patients with SPS and history of DVT and 101 healthy individuals. We were interested in 2 SNPs within platelet endothelial aggregation receptor 1 (PEAR1) gene (rs12041331 and rs12566888), 2 SNPs within mkurine retrovirus integration site 1 gene (rs7940646 and rs1874445), 1 SNP within Janus kinase 2 gene (rs2230722), 1 SNP within FCER1G gene (rs3557), 1 SNP within pro-platelet basic protein (rs442155), 4 SNPs within alpha2A adrenergic receptor 2A (ADRA2A; rs1800545, rs4311994, rs11195419, and rs553668), and 1 SNP within sonic hedgehog gene (rs2363910)...
January 1, 2018: Clinical and Applied Thrombosis/hemostasis
Soo-Jeung Park, Dasom Lee, Minhee Lee, Han-Ol Kwon, Hyesook Kim, Jeongjin Park, Woojin Jeon, Minseok Cha, Suhwa Jun, Kwangjin Park, Jeongmin Lee
The immune response is stimulated to protect the body from external antigens and is controlled by several types of immune cells. In the present study, the immunomodulatory effects of Curcuma longa L., purple sweet potato, and mixtures of the two (CPM) were investigated in C57BL/6 mice infected with LP-BM5 murine leukemia virus (MuLV). Mice were divided into seven groups as follows: normal control, infected control (LP-BM5 MuLV infection), positive control (LP-BM5 MuLV infection+dietary supplement of red ginseng 300 mg/kg body weight), the original powder of C...
June 4, 2018: Journal of Medicinal Food
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