Adenoviruses cause respiratory and enteric nomenclature were adopted in , acknowledging the infections in humans original source of the virus from adenoid tissue. Originally and incor- be oncogenic. Although no evidence has linked adeno- rectly postulated to be a cause of the common cold, viruses to human cancer, these viruses have been used as adenoviruses were subsequently shown to be respon- models for understanding the molecular biology of can- sible for a number of other respiratory syndromes cer.
Furthermore, their study has helped uncover basic including pneumonia; they can also cause eye and gastro- mechanisms of gene expression in mammalian cells. The current adenovirus name and In , the laboratories of Philip Sharp and Richard. Roberts discovered RNA splicing by studying adenovi- constructed from two basic building blocks, the hexon rus late mRNAs, and were jointly awarded the Nobel and the penton base Figure A total of hexons cover the 20 faces II in vitro, and he and others subsequently discovered many of the protein factors involved in transcription in mammalian cells by using this model system.
Human adenoviruses have recently become of great importance as gene therapy vectors and are one of several promising new oncolytic virus anticancer agents. The known adenoviruses include 50 human virus serotypes, distinguished by their sensitivity to neutralizing antibodies.
This chapter will deal with the best-studied human adenoviruses: types 2 and 5, non-oncogenic members of group C, and type 12, a highly oncogenic member of group A. Virions have icosahedral symmetry and are studded with knobbed fibers Adenovirus virions have a remarkable resemblance to a Figure A computer-generated regular icosahedron, with 20 equilateral triangular faces image of adenovirus type 2 virion, viewed along a threefold and 12 vertices Figures This hand- symmetry axis.
Reconstructed from cryoelectron microscopy some capsid contains a total of 11 viral proteins, but is images. Figure A schematic cross-sectional view of a human adenovirus type 5 virion, with components shown as indicated. They localize at to the penton base at one end and has a terminal knob nuclear pores where they are disassembled in a sequen- at the other end.
A kDa virus-coded ter- Expression of adenovirus genes is controlled minal protein is covalently linked via a serine residue to at the level of transcription each of the 5' ends of the viral DNA Figure Although the adenovirus gene map Figure This ponent parts it is easier to understand. Eight transcriptional promoters are used by allowing single DNA strands to circularize, forming cellular RNA polymerase II to initiate transcription, a short panhandle end.
Transcription units can be divided into three classes, depending on the timing of their use during the infec- tious cycle. Most adenovirus serotypes, as named IX and IVa2. Note that these genes use distinct well as Coxsackievirus B3 a picornavirus; see Chapter promoters but share polyadenylation sites in common 11 utilize the same receptor on human cells, termed with E1B and E2B.
There is only one late transcription Coxsackievirus and adenovirus receptor CAR. Rodent cells also possess Each of the 13 families of viral genes contains a a closely related CAR protein that allows their infection variety of often overlapping protein-coding regions. The penton base be seen as constructed from modular units similar to binds to these integrins via a domain similar to that used the early and late transcription units of the smaller and by extracellular adhesion molecules that interact with simpler polyomaviruses Chapter Adenovirus tran- integrins.
Binding to integrins leads to the migration of scription units are interspersed in such a way that virtu- virus-receptor complexes to clathrin-coated pits, where ally all of the viral genome is utilized for coding proteins they are taken up into endosomes see Chapter 4.
Terminal protein shown as an orange square. Rightward reading transcripts shown at top, leftward reading transcripts shown at bottom. Vertical bars show 5' ends of RNAs, corresponding to transcriptional promoters; arrowheads represent 3' ends of mRNAs, corresponding to polyadenylation sites. Introns are shown as interruptions in mRNAs.
Adenovirus genomes also contain one or two copies alternative splicing. The natural target cells of adenoviruses are acts see Chapter Adenoviruses rely on a variety of host proteins for opti- mal DNA replication and production of adequate levels E1A proteins are the kingpins of the of precursor deoxynucleotides. The E1A non-dividing cells to enter the S, or DNA synthesis, promoter, located near the left end of the genome phase of the cell cycle.
An unintended result is the Figure Viruses cells and to induce tumor formation in experimental that contain mutations in E1A genes make strongly animals, thus making E1A an oncogene. E1A proteins bind to the retinoblastoma Two major E1A RNAs, denoted 13S and 12S for protein and activate E2F, a cellular their slightly different sedimentation rates in sucrose transcription factor gradients , encode proteins of and amino acid residues, respectively R and R; Figure How do E1A proteins induce cells to enter the S These two proteins are identical except for a amino phase of the cell cycle?
The best-understood mecha- acid region in the R protein that is missing in the nism involves an interaction between E1A proteins R protein because of removal of a longer intron by and the retinoblastoma Rb family of cellular tumor. Reading frames for the amino acid and amino acid protein products are shown boxes with the critical amino terminal region N and conserved regions CR1, 2, and 3. In the G1 phase of normally cycling cells, represses activates Rb becomes phosphorylated by cyclin-dependent E1A protein kinases Cdks , and the phosphorylated Rb no S phase genes S phase and Ade n E2 genes longer binds to E2F.
Thus free of repression, E2F can infec ovirus activate expression of S-phase genes, allowing progres- tion Rb sion into S phase. E2F is therefore free to activate genes, and bound histone deacetylase HDAC represses transcription of its target genes Figure At the transcription by altering chromatin structure. This complex same time, E2F activates both viral genes E2A and E2B is disrupted either during the cell cycle, by phosphorylation of by binding to a site near their common promoter.
This Rb by cyclin-dependent kinase Cdk; above , or during infec- leads to production of three early viral proteins that tion, by binding of adenovirus E1A proteins below , allowing direct adenovirus DNA replication.
E2F to transcriptionally activate cellular and viral genes. E1A proteins also activate other cellular transcription factors suppressor proteins Figures Proteins of the Rb scription of adenovirus E3 and E4 genes by interactions family bind to and inactivate a family of cellular tran- between its unique CR3 domain and cellular tran- scription factors, termed E2F. These interactions stabilize the transcription complex signal to the cell that something is wrong, and activated and stimulate viral gene expression.
Finally, the E1A amino terminus and part of CR1 Apoptosis is a regulated form of cell suicide invoked engage in a complex with a distinct set of cellular pro- when cells undergo extensive DNA damage, virus teins, the histone acetyl transferases. These enzymes, infection, or other insults.
Mdm-2 binds to p53 and targets role in the transcriptional activation of large blocks of it for ubiquitin-mediated degradation, whereas p14Arf cellular genes. This is carried out via the acetylation binds to Mdm-2 and blocks its binding to p53, thus of nucleosomal histones and other proteins, resulting in stabilizing p First, by binding to Rb factors and is more easily transcribed.
Thus these pro- Figure As a result, increased histone deacetylases referred to above. Binding of E1A levels of p14Arf bind to Mdm-2 and reduce its level in proteins to histone acetyl transferases increases histone the cell. Mdm-2 gene, further reducing the level of Mdm The resulting accumulation of p53 could induce the early death of infected cells by apoptosis and severely E1A proteins indirectly induce apoptosis limit virus production were it not reversed by other by activation of cellular p53 protein adenovirus gene products, particularly two E1B proteins.
Expression of E1A proteins leads indirectly to stabili- zation and activation of the cellular tumor suppressor E1B proteins suppress E1A-induced apoptosis protein, p53 Figure The two best characterized proteins, denoted 19K and 55K for their molecular weights , are E1A produced from a single 2. Activates transcription The 19K protein is a functional homologue of the cellular protein Bcl-2, which is a suppressor of apopto- sis. Oligomers of another Bcl-2 family member, called p14Arf Bax, stimulate the caspase cascade and lead to apoptotic E1A cell death see Figure Bcl-2 reverses this effect Activates by binding to Bax, preventing oligomer formation.
Blocks p53 activation transcription Binds to Mdm-2 Both Bcl-2 and Bax are associated with mitochondrial membranes in a complex that regulates apoptosis. The adenovirus 19K protein mimics Bcl-2 by binding to Bax p53 Mdm-2 and preventing oligomer formation, thereby blocking apoptosis Table Binds to p53 The 55K protein binds directly to p53 and blocks transcription from pdependent promoters, p53 therefore inhibiting pdependent apoptosis.
A growing list of other key Figure See text for details. Table Thus the two major E1B proteins protect infected which is then coated with the single-stranded DNA bind- cells from both pdependent and pindependent ing protein.
Synthesis proceeds to the end of the linear apoptosis, reversing activities stimulated by E1A proteins. DNA, producing a double-stranded progeny DNA con- This allows the cell to survive long enough to produce taining a parental and a daughter strand, and a displaced high levels of progeny adenovirus virions before parental single-stranded DNA molecule step 3.
Single-stranded DNA is circularized The preterminal protein primes DNA synthesis via the inverted terminal repeat carried out by viral DNA polymerase At this point the double-stranded progeny DNA can Once E1A has induced the cell to enter S phase and the serve as a template for further replication, but in each early viral gene products have accumulated, viral DNA round only one double-stranded DNA molecule is replication begins.
Three essential proteins made by E2 formed, and there would therefore be no net accumula- genes carry out viral DNA replication. A single-stranded tion of viral DNA. This stem recre- linear DNA molecule Figure Therefore, nal repeat, contain binding sites for a complex between the DNA polymerase-preterminal protein complex can the adenovirus DNA polymerase and preterminal pro- bind and initiate DNA replication step 5.
DNA viruses or a DNA primer used by parvoviruses , In an alternative pathway not shown , replica- adenoviruses use the preterminal protein as a primer tion can begin at both ends of a double-stranded for replication.
This protein contains a serine residue DNA molecule, as both ends are identical. This also whose hydroxyl group forms a phosphodiester bond gives rise to two progeny genomes, as the DNA poly- with deoxycytidine, in a reaction that cleaves dCTP to merase molecules pass each other on the comple- dCMP. This covalently bound dC residue is then used mentary DNA strands like trains on separate tracks. During the early phase this promoter has a low activity, and the rare transcripts terminate prema- turely, so that only low levels of L1 mRNAs are made.
Second, polypeptide IVa2, which is encoded by an intermediate C G gene, binds to viral DNA at a site shortly downstream of 4 the position where late transcription begins. IVa2 coop- erates with factors bound to an upstream enhancer to activate transcription.
Together, these steps activate the major late promoter by a factor of or more. Each primary transcript from C the major late promoter is cleaved at only one of these sites, and the resulting polyadenylated RNA is spliced C in a complex fashion to generate one of the 18 possible G late mRNAs.
C G G C Figure First, all late mRNAs represented by a black square. Newly synthesized DNA are made by turning on a single, highly active promoter, is shown in blue. Major late promoter Transcription. Poly A addition at one of 5 possible sites. Cap An Cap An. Cap An Tripartite leader Figure Transcription initiates at the major late promoter, and the RNA is cleaved and polyadenylated at one of 5 possible sites. The tripartite leader is formed by splicing 3 small exons; it is spliced to the mRNA body at one of several alternative 3' splice sites.
Exons are shown as shaded rectangles. EIF4F is their 5' ends. Condition: New. Language: English. Brand new Book. Netesov and others published Introduction to molecular virology Find, read and cite all the research you need on ResearchGate molecular virology book.
Health Details: PDF. Part I. Front Matter. This book is printed on acid free paper. Our company is built on a foundation of principles that include responsibility to the communities we serve and where we live and work.
In , we launched a Corporate Citizenship Initiative, a global effort to address the environmental, social, economic, and ethical challenges we face in our business. For more information, please visit our website: www.
Comparative Plant Virology provides a complete overview of our current knowledge of plant viruses, including background information on plant viruses and up-to-date aspects of virus biology and control. It deals mainly with concepts rather than detail.
The focus will be on plant viruses but due to the changing environment of how virology is taught, comparisons will be drawn with viruses of other kingdomes, animals, fungi and bacteria. It has been written for students of plant virology, plant pathology, virology and microbiology who have no previous knowledge of plant viruses or of virology in general.
Advanced undergraduate and graduate students in basic and applied plant virology, plant pathology, microbiology, genetics and molecular biology, biological control, ecology, evolution, and related aspects of plant science.
Suspicion was the order of the day. Download Product Flyer. This is a dummy description. Two distinct groups of viruses are pathogenic in humans: hiv-1 and hiv Both are transmitted sexually and known to cause immunodeficiency disease. Hiv enters the cell through use of the cd4 receptor and chemokine co-receptors, primarily ccr5 and cxcr4. Introduction to structural and molecular virology yaroslav daniel bodnar university of illinois at urbana-champaign viruses highlight some big ideas structure-dynamics-function relationships.
Atomic structure of a rhinovirus C, a virus species linked to severe. Atomic structure of a rhinovirus C, a virus species linked Search for new physics with atoms and molecules. COVID how physics is helping the fight against the pandemic. Editors: Mateu, Mauricio G. Free Preview. Kinetic class virology Title List.
0コメント