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Cell and Systems Biology
Mounir Abou Haidar

1Lecture 1Introduction to Viruses Definition of a virus 1 Lwoff strictly intracellular and potentially pathogenic entities with an infectious phase and a Possessing only one type of nucleic acid RNA or DNA b Multiplying in the form of their genetic material c Unable to grow and to undergo binary fission d Devoid of a Lipmann system no enzymes to make their own ATP because they are tinywhy that need a living cell 2 A virus isa A tiny submicroscopic particleb capable of multiplying in living cells and organisms inducing in them different kinds of illnesses c attack all living organisms man animals insects plants bacteria3 Goodheart 1969 A virus4 a Consists of genetic matrial enclosed in a protective coating b One of the simplest entities able to reproduce c No metabolic systems no intrinsic mobility cannot respond to stimuli do not grow in the usual sense d Ability to maintain genetic continuity with the possibility of mutationonly basis for considering viruses to be alive e Mechanism by which viruses reproduce is unique the genetic material of the virus becomes a functional part of the cell it has infected f The genes added to the cell by the virus caused the infected cell either to produce more virus particles with cell death usually the end result or to become changed and acquire new characteristics Distinctive properties of viruses in comparison to other infectious agents 1 Smaller 2 Simpler in general they consist of 2 substances a nucleic acid which contains the genetic info of the virus and a protein to coat the nucleic acid and protect it 3 Unable to multiply outside a living cell a Cannot multiply in chemically defined solution b Replicate only inside living cells making use of the internal cellular environment c Only within the nuclei mitochondria ribosomes and cytoplasmic components does a virus show characteristics of a living moleculeabsolute parasitism2Lecture 23Composition of viruses 2 types 1 Helical 2 Icosahedral Virus compositionIn general viruses are composed of either RNA or DNA NEVER BOTH and are covered by one or several types of proteinSome types also contain lipids or carbohydratesNucleic acidsproteins in viruses are NOT covalently linked but stabilized by hydrogen ionic Van der Waals hydrophobic and other weak bonds Viral Nucleic AcidsFormed of 3 types o Heterocyclic nitrogenous base o A sugar o A phosphateRNA A G C UriboseDNA A G C Tdeoxyribose 2CGlycosidic bond links NHgroup in position 9 of purines and position 1 of pyrimidines to position 1 of the sugarThe phosphates link the bases on the sugar in positions 3 and 5 ester bondSome have circular DNAMost are linearRibosomes start at 5Polymerase start at 3CG has 3 bondsmore stable and strongerSome viruses contain modified bases o Eg some have a 5 end which is capped with a methylated guanine in position 7 m7gsense RNA o Have the cap except polio o Directly translatable by ribosomes o 5 cap is a signal for ribosomes sense RNA o Not directly translatable by ribosomes o Have a polymerase which will make a complement strand in the cell which is translatable RNA Nucleic Acid EnzymesDNA and RNA polymeraseso Necessary for viral replication o Add a nucleotide to the 3 OH end of a growing strand of DNA or RNA o Sequence determined by template strand of DNARNARNA polymerase DO NOT require a primerDNA polymerase DO require a primer small strand of DNARNA which is hybridized to the template strandMOST but not all viruses code for their own polymeraseALL polymerase have helicase activity an enzyme used to unwind dsDNARibosomes do not have helicase activitycant translate dsDNAdsRNAGenomes are dsantiparallel soend of one strand blocks ribosomes Classes of Viral Polymerases transcriptionDNAdependent RNA polymerase o DNAmRNA 3 RNAdependent RNA polymerase o RNAmRNARNAdependent DNA polymerase reverse transcriptase o RNADNARNADNA hybridRNA degrades by RNAase activityssDNADNAdependent DNA polymerasedsDNADNAdependent DNA polymerase o Encoded by most DNA viruses for their own replication Modifying EnzymesMethylase transfer methyl from adenosylmethionine to a nitrogenous base o Most mRNAs and manysense RNA viruses have a capped 5 terminus which has been modified by a methylase o Functions of a 5 capPrevention of degradation by exonucleasesPromotion of translation of mRNAs and viralRNANuclease capable of cleaving phosphodiester bonds between the nucleotide subunits of nucleic acids cut nucleic acids o Endonuclease vs exonuclease o Ribonuclease vs deoxyribonucleaseLigase catalyze the joining of 2 large molecules by forming a new chemical bond usually with accompanying hydrolysis of a small chemical group dependent on one of the larger molecules There are RNA and DNA ligasesRestriction enzymes cut sugatphosphate backbones DNA fragment added from another molecule cut by same enzyme Base pairing occurs and DNA ligase seals itViral ProteinsGeneral description o Formed of long chains containing smaller components the aa o Proteins are products of nucleic acids aa sequences determined by sequence of nucleotides on a nucleic acid o Viral proteins can be structural capsid protein envelope protein or nonstructural enzymatic Some of these viral enzymes could be packaged in virus particlesMajority are notLevels of protein structure o Prions are rich of betasheet which is protease resistant 1 Primary order of aa 2 Secondary helical configuration of peptide chain 3 Tertiary the 3D folding of the peptide chainfunctional 4 Quarternary theand spatial relationship of repeating subunits o Primary structure is stable due to peptide bonds which are covalent bonds o The rest are formed of weaker noncovalent bonds such as Hbonds ionic bonds hydrophobic bonds and van der Waals forcesSome functions of viral proteins 1 Form structure of virus and protect the genetic material 2 Specific attachment of a virus particle to a receptor site on cell surface 3 Viruses are good antigens When introduced into a vertebrate they elicit the production of antibodies antigenic sites 4 In plant viruses the capsid protein may also be involved in replication and transport cell to cell movement 5 Capsid protein may play a regulatory role in the life cycle and symptoms development plants 6 Many other functions are carried out by enzymes coded for by the viral genome o Polymerase movement proteins only plants integrases o Some will form glycoproteins o
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