Replicative cycle As obligate intracellular parasites, Virus must enter and replicate in living cells in order to reproduce themselves. This growth cy

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2 Replicative cycle As obligate intracellular parasites, Virus must enter and replicate in living cells in order to reproduce themselves. This growth cycle involves specific attachment of virus, penetration and uncoating, nucleic acid transcription, protein synthesis, maturation and assembly of the virions and their subsequent release from the cell by budding or lysis

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8 Attachment/Adsorption

9 Attachment/ Adsorption

10 Attachment/Adsorption Virus Target Cell Receptor Epstein-Barr virus B lymphocyte CR2 (CD21) receptor (complement) Human immunodeficiency virus T lymphocyte CD4 molecule and chemokine coreceptors Rhinovirus Epithelial cells ICAM-1 (protein from immunoglobulin superfamily) Poliovirus Epithelial cells protein from immunoglobulin superfamily Rabies virus Nerve cells acetyl choline receptor Influenza A Epithelial cells Sialic acid B19 parvovirus Erythroid precursor cells Erythrocyte P antigen (globozid)

11 PENETRATION (Virus enters the cell)! " # $

12 Fusing # % &

13 Fusing herpesviruses, paramyxoviruses, HIV 13

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15 Endocytosis '# 15

16 Enveloped viruses Some enveloped viruses require an acid ph for fusion to occur and are unable to fuse directly with the plasma membrane. These viruses are taken up by invagination of clathrin coated pits into endosomes. As the endosomes become acidified, the latent fusion activity of the virus proteins becomes activated by the fall in ph and the virion membrane fuses with the endosome membrane. This results in delivery of the internal components of the virus to the cytoplasm of the cell

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19 Non-enveloped viruses $ (

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21 UNCOATING $ ) & # *+,%# -! "

22 BIOSYNTHESIS $

23 The Baltimore classification system Based on genetic contents and replication strategies of viruses, viruses are divided into the following seven classes: 1. dsdna viruses 2. ssdna viruses 3. dsrna viruses 4. (+) sense ssrna viruses (codes directly for protein) 5. (-) sense ssrna viruses 6. RNA reverse transcribing viruses 7. DNA reverse transcribing viruses

24 The Baltimore classification system Incomplete ssdna ssdna +RNA dsdna - RNA mrna +RNA dsrna

25 DNA replication Limits of DNA polymerase III can only build onto 3 end of an existing DNA strand 3 5 Okazaki fragments 3 5 ligase Okazaki Lagging strand 5 growing replication fork 3 Leading strand 3 5 Lagging strand Okazaki fragments joined by ligase DNA polymerase III Leading strand continuous synthesis 3

26 DNA replication growing replication fork 3 DNA polymerase III RNA 5 RNA primer serves as starter sequence for DNA polymerase III 3

27 DNA replication DNA polymerase I removes sections of RNA primer and replaces with DNA nucleotides DNA polymerase I ligase 5 growing replication fork 3 RNA 5 3

28 RNA replication

29 mrna Processing Exon 1 DNA Transcription Pre mrna Exon 2 Exon 3 intron 1 Exon intron 2 Exon 5 3 Start Codon m7 G-P-P-P- Exon 1 Exon 1 m7 G-P-P-P- intron 1 m7 G-P-P-P- intron 1 Exon 2 Exon 2 Protein-coding Region Exon 1 Exon 2 intron 2 Exon 3 intron 2 Exon 3 Exon 3 Mature mrna leaves for cytoplasm In nucleus Add 5 5 cap Cleave at 3 3 end Add 3 3 poly-a A tail AAAAAA.. Stop Remove Introns Codon Splice Exons together AAAAAA

30 The Baltimore classification system

31 Flow of events - replication of herpesviruses "#$"%& % $%& '$'& "%( %( '(!

32 The Baltimore classification system

33 Flow of events - replication of parvoviruses Adsorption Penetration Decapsidation Nucleus Translation mrna Conversion to dsdna Transcription Genome replication Viral Proteins Assembly Release

34 The Baltimore classification system

35 Flow of events - replication of reoviruses Adsorption and penetration Adsorption and penetration mrna Late transcription and translation Nucleus Translation Assembly Transcription Release Provirus assembly

36 The Baltimore classification system ) ) * + (,

37 Flow of events - replication of picornaviruses Adsorption and penetration Decapsidation Nucleus Translation polymerase Genome replication Cleavage of poliprotein Assembly and release

38 The Baltimore classification system # # -. /.!,

39 Flow of events - replication of orthomyxoviruses Adsorption Penetration Transcription Decapsidation (5 cap-mrna-polya) 10 Genome replication ((+)RNA) 8 Translation Nucleus Assembly Release

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41 Flow of events - replication of retroviruses Adsorption Reverse transcription Penetration Translation Incomplete decapsidation Nucleus Integration of proviral dsdna Transcription Genome replication Protein glycolization Protein glycolization Assembly Maturation Release

42 The Baltimore classification system "

43 Flow of events - replication of Hepadnaviruses $)& ( $)&. %!!

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45 Maturation The stage of viral replication at which a virus particle becomes infectious; nucleic acids and capsids are assembled together.

46 ASSEMBLY The stage of replication during which all the structural components come together at one site in the cell and the basic structure of the virus particle is formed.

47 RELEASE Disintegration : naked virus cause the host cell lysis Budding: enveloped viruses Budding viruses do not necessarily kill the cell. Thus, some budding viruses may be able to set up persistence

48 RELEASE Cell lysis Budding

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51 There are two important variation which relate well with medical practices Antigenicity variation: In most viruse the antigenicity is stable but in some viruses such as influenze virus the antigenicity may vary and cause the disease to epidemic. Virulence variation(virulent viruses): Less virulent viruses always used in prevention.