* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download mv-lect-06-virus-repl-stratigies
DNA polymerase wikipedia , lookup
Mitochondrial DNA wikipedia , lookup
Human genome wikipedia , lookup
Cre-Lox recombination wikipedia , lookup
Metagenomics wikipedia , lookup
DNA supercoil wikipedia , lookup
Genome evolution wikipedia , lookup
Epigenetics of human development wikipedia , lookup
Short interspersed nuclear elements (SINEs) wikipedia , lookup
No-SCAR (Scarless Cas9 Assisted Recombineering) Genome Editing wikipedia , lookup
History of genetic engineering wikipedia , lookup
Microevolution wikipedia , lookup
Therapeutic gene modulation wikipedia , lookup
Artificial gene synthesis wikipedia , lookup
Viral phylodynamics wikipedia , lookup
Genomic library wikipedia , lookup
Messenger RNA wikipedia , lookup
Non-coding DNA wikipedia , lookup
Polyadenylation wikipedia , lookup
Extrachromosomal DNA wikipedia , lookup
RNA interference wikipedia , lookup
Nucleic acid tertiary structure wikipedia , lookup
Nucleic acid analogue wikipedia , lookup
RNA silencing wikipedia , lookup
History of RNA biology wikipedia , lookup
Epitranscriptome wikipedia , lookup
Non-coding RNA wikipedia , lookup
Deoxyribozyme wikipedia , lookup
VIRUS REPLICATION STRATEGIES Dr. Sobia Manzoor MV, Lecture 06 Introduction • Replication of genetic information is the single most distinctive characteristic of living organisms, which is accomplished with great economy and simplicity among viruses. • To achieve the expression, replication, and spread of their genes, different families of viruses have evolved diverse genetic strategies and life cycles that exploit the biology and biochemistry of their hosts in a variety of ways. • Each infection represents an encounter between the genetic program of a virus and that of its host, defining host-viral relationships. • This also create opportunities for the rational development of antiviral drugs and for domesticating viruses as expression vectors, live attenuated vaccines, and pesticides. Diversity of Viral Genome Structures • • • • • Different families of viruses have different genomes: Double-stranded (ds) / single-stranded (ss) viruses DNA / RNA viruses positive, negative, or mixed (ambisense) polarity linear or circular topology single or multiple segments The coding strategies of arenaviruses (family Arenaviridae) and members of the Phlebovirus genus of the Bunyaviridae differ from those of other negative-sense RNA viruses in that some proteins are coded in viral-complementary RNA sequences and others are coded in the viral RNA sequence. The term ambisense RNA has been proposed to denote these unique coding arrangements. • Each variation has consequences for the pathways of genome replication, viral gene expression, and virion assembly. • Viral taxonomy above the family level is variable, with only 10 of 71 virus families being assigned to the three orders that are currently recognized. Families and Genera of Viruses that Infect Vertebrates Genome Virus Family Adenoviridae Polaritya dsDNA Both Topologyb Linear Anellovirus genus ssDNA Negative Asfarviridae dsDNA Circoviridae Type Genome Replication Segments 1 Enzyme Viral DdDp Intracellular Site Nucleus Circular 1 Cellular DdDp Nucleus Both Linear 1 Viral DdDp Cytoplasm ssDNA Negative/ ambisense Circular 1 Cellular DdDp Nucleus Hepadnaviridae dsDNA Both Linear 1 Virion RTase Nucleus/cytoplasm Herpesviridae dsDNA Both Linear 1 Viral DdDp Nucleus Iridoviridae dsDNA Both Linear 1 Viral DdDp Nucleus/cytoplasm Papillomaviridae dsDNA Both Circular 1 Cellular DdDp Nucleus Parvoviridae ssDNA Either Linear 1 Cellular DdDp Nucleus Polyomaviridae dsDNA Both Circular 1 Cellular DdDp Nucleus dsDNA Both Linear 1 Viral DdDp Cytoplasm Arenaviridae ssRNA Ambisense Linear 2 Virion RdRp Cytoplasm Arteriviridae ssRNA Positive Linear 1 Viral RdRp Cytoplasm Astroviridae ssRNA Positive Linear 1 Viral RdRp Cytoplasm Birnaviridae dsRNA Both Linear 2 Virion RdRp Cytoplasm Bornaviridae ssRNA Negative or ambisense Linear 1 Virion RdRp Nucleus Bunyaviridae ssRNA Negative Linear 3 Virion RdRp Cytoplasm Caliciviridae ssRNA Positive Linear 1 Viral RdRp Cytoplasm Coronaviridae ssRNA Positive Linear 1 Viral RdRp Cytoplasm Deltavirus genus ssRNA Negative Circular 1 RNA pol II Nucleus Filoviridae ssRNA Negative Linear 1 Virion RdRp Cytoplasm Flaviviridae ssRNA Positive Linear 1 Viral RdRp Cytoplasm Hepevirus genus ssRNA Positive Linear 1 Viral RdRp Cytoplasm Nodaviridae ssRNA Positive Linear 2 Viral RdRp Cytoplasm Orthomyxoviridae ssRNA Negative Linear 6-8 Virion RdRp Nucleus Paramyxoviridae ssRNA Negative Linear 1 Virion RdRp Cytoplasm Picornaviridae ssRNA Positive Linear 1 Viral RdRp Cytoplasm Reoviridae dsRNA Both Linear 10-12 Virion RdRp Cytoplasm Retroviridae ssRNA Positive Linear 2 identical Virion RTase Nucleus/cytoplasm Rhabdoviridae ssRNA Negative Linear 1 Virion RdRp Cytoplasm Togaviridae ssRNA Positive Linear 1 Viral RdRp Cytoplasm Viral Pathways and Enzymes • As intracellular parasites, all viruses depend heavily on functions provided by their host cells. • Nevertheless, almost all viruses encode and express unique proteins including enzymes, and many viruses exploit pathways of information transfer. • This is particularly evident among the RNA viruses. Variation In Replication Strategies Whatever the structure and replication strategy of their genomes, all viruses must express their genes as functional mRNAs early in infection in order to direct the cell's translational machinery to make viral proteins. mRNA Complement positive sense negative sense RNA Viruses These viruses replicate their genomes via one of two unique biochemical pathways: • RNA-dependent RNA synthesis (RNA replication), • RNA-dependent DNA synthesis (reverse transcription) followed by DNA replication and transcription. Both pathways require enzyme activities that are not usually found in uninfected host cells and must therefore be encoded in the viral genome and expressed during infection. In some families of RNA viruses, the corresponding polymerase and other associated enzymes with the viral genome are co-packaged during the viral assembly. DNA viruses • Most DNA viruses undergo transcription, replication and assembly in the nucleus, the site of cellular DNA transcription and replication. • The exceptions are the poxviruses, iridoviruses, and African swine fever virus, which replicate their DNA genomes partly or completely in the cytoplasm • In contrast, most RNA viruses replicate in the cytoplasm. • Retroviruses integrate DNA copies of their genomes into cellular chromosomes. • Other notable exceptions are the orthomyxoand bornaviruses, whose linear negative-sense RNA genomes replicate in the nucleus. • The circular RNA genome of hepatitis delta virus also replicates in the nucleus. • Pathways of primary mRNA synthesis by DNA viruses of animals • ds DNA ss DNA Cellular DNA Polymerase Cellular RNA Pol II mRNA + Pathways of primary mRNA synthesis by DNA viruses of animals. *Hepadnaviruses replicate via reverse transcription of an ssRNA intermediate ds DNA Cellular RNA Pol II Evasion of Host Cell Defense • Many viruses express gene products that act to circumvent one or more of the several different antiviral defense mechanisms developed by host organisms . • Host defense mechanisms can be innate or adaptive. • Innate mechanisms involve apoptosis, interferon production and RNA interference . • Adaptive mechanisms of immunity include the celland antibody-mediated immune responses • In different viruses, different mechanisms inhibit apoptosis, intercept/suppress interferon, obstruct RNA interference, and either evade or suppress different arms of the adaptive immune response. • Pathways of primary mRNA synthesis by RNA viruses of animals • Pathways of primary mRNA synthesis by RNA viruses of animals. How RNA viruses produce mRNA at the start of infection depends on the nature of the viral genome. ds, double stranded; ss, single stranded. RNA Replication Is Error Prone • The polymerases that catalyze RNA replication and reverse transcription have minimal proofreading activities. • Error rates are about 10,000 times higher than those encountered during DNA replication. • RNA viruses can evolve up to 1 million times faster than DNA-based organisms Quasispecies • A quasispecie provides a fertile source of phenotypic variants that can respond rapidly to changing selection pressures by shifting its composition. Levels of Segmentation Genes, mRNA and Proteins Viral RdRps generally appear somewhat restricted in their ability to access internal promoter sites on RNA templates, within the host cells. Through evolution, different RNA virus families have found three solutions: • Proteolytic processing of poly protein precursors to derive final protein products. e.g. the picorna-, toga-, flavi-, and retrovirus families • In some other systems, different cis-acting RNA signals are largely responsible for determining the relative template activities of the complementary strands. However, different host factors are involved here as well. • Unlike the enzymes that replicate DNA that usually require primers, most RdRps can initiate RNA synthesis de novo. • However, there are exceptions: Picornavirus RdRps use a small viral protein (Vpg) that is first covalently uridylated, and then used as a primer for viral RNA synthesis. • In another mechanism of priming, the enzymes encoded by orthomyxo- and bunyaviruses cleave short capped oligonucleotides from host mRNAs and use them to prime transcription.