VIRAL STRUCTURE. Nucleic acid: Either DNA or RNA Single-stranded or double-stranded Linear or circular Segmented or non-segmented

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1 VIRUSES non-cellular, obligately intracellular parasites replicate not by division characteristic intracellular life cycle (eclipse period) infectious genetic information

2 VIRAL STRUCTURE Nucleic acid: Either DNA or RNA Single-stranded or double-stranded Linear or circular Segmented or non-segmented Capsid: Composed of protein Structural units: capsomers Different types of symmetry (helical, icosahedral, complex)

3 Icosahedral (cubical) symmetry

4 Helical symmetry

5 Complex symmetry Pox viruses

6 Envelope: Present or absent depending on virus family Lipoprotein membrane Originate from cellular membranes (cytoplasmic, nuclear, intracytoplasmic) Contain virus encoded glycoproteins Enveloped viruses are more sensitive

7 Classification of viruses Virus classification based on: Type of nucleic acid: ssdna, dsdna, ss(-)rna, ss(+) RNA, dsrna Size and symmetry of nucleocapsid Presence of envelope Genome organisation and relatedness Antigenic properties Biological properties (host range, tissue tropism, pathology)

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9 Replication of viruses Only inside living cells (obligately intracellular) Characteristic intracellular replication cycle Details are variable depending mainly on the viral genome: ds DNA, ssdna, ss (+) RNA, ss (-) RNA, ds RNA

10 Virus replication: single burst

11 General scheme of replication

12 Adsorption (attachment) The virus becomes attached to the cells. Adsorption occurs to specific cellular receptors ( glycoproteins, phospholipids, glycolipids). Presence of receptor is an important determinant of host and cell specificity. Attachment is blocked by antibodies that bind to the viral sites involved (virus neutralisation).

13 Virus Receptors Many examples of virus receptors are now known. Schematic representation of some virus receptors - arrows indicate virus attachment site:

14 Penetration Penetration normally occurs a shortly after adsorption. Penetration is generally an energy-dependent process. Three main mechanisms are involved: 1. translocation 2. endocytosis 3. membrane fusion

15 Translocation 1)Translocation of the entire virus particle across the cytoplasmic membrane of the cell. This process is relatively rare among viruses & is poorly understood.

16 The most common mechanism of virus entry into cells. This step does not require any specific virus proteins Receptor-mediated endocytosis is an efficient process for taking up extracellular macromolecules. Endocytosis

17 Fusion Fusion of the virus envelope (enveloped viruses only) Occurs either with the cell membrane (directly at the cell surface) or with a vesicular membrane (after endocytosis). Fusion requires the presence of a specific fusion protein in the virus envelope (e.g. influenza haemagglutinin)

18 Uncoating The virus capsid is completely or partially removed & the virus genome exposed, usually in the form of a nucleoprotein complex. Uncoating may occur simultaneously with penetration (membrane fusion) In certain cases, desintagration of the virion is not complete (e. g. Rotavirus).

19 Viral Nucleic Acid Replication and gene expression DNA viruses Except for poxviruses, transcription and replication occur in the nucleus, and translation in the cytoplasm. For most DNA viruses, only a part of the genome is transcribed into early messengers. The synthesis of early or regulatory proteins is the key initial step in viral DNA replication. After DNA synthesis, the remainder of the genome is transcribed into late messengers encoding for late or structural proteins.

20 Herpesvirus replication

21 Immediate early Early Late ds DNA genome: Herpesviruses

22 Hepadna (HBV)

23 Viral Nucleic Acid Replication and gene expression RNA viruses Virus encoded RNA polymerases are needed Takes place usually in the cytoplasm (exceptions: influenza virus, retroviruses) Replication consists of building a complementary to the viral strand of the same length, which then servers as the template for progeny viral genomes. Some viruses carry the virus encoded RNA polymerases within the virions, while others synthesize them in the infected cells.

24 ss (+) RNA: polycistronic mrna (Picornaviruses) protease

25 ss (+) RNA: complex transcription (Togaviruses)

26 ss (-) RNA genome A: Orthomyxoviruses B: Paramyxoviruses

27 L RNA Arenaviridae - replication Z L 5 3 S RNA genome S RNA antigenome GPC NP replikáció - transzkripció + transzkripció NP mrns 3 cap-5 5 GPC mrns 5 -cap 3 Ambisense genome: partially +, partially -

28 ds RNA genome: Reoviruses

29 Retroviruses (HIV)

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31 Maturation and Release of Naked Icosahedral Viruses Preassembled capsomers are joined to form empty capsids (procapsid) which are the precursors of virions. Viral genome is encapsidated. Release is accompanied usually with death and lysis of the infected cell.

32 Maturation and Release of Enveloped Viruses Viral proteins are first associated with the nucleic acid to form the nucleocapsid. Nucleocapsid is then surrounded by an envelope (plasma membrane, ER, Golgi). The envelope always contains important viral antigens. The carbohydrates and the lipids in the envelope are produced by the host cell.

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34 PATHOGENESIS OF VIRAL INFECTIONS The infected cell Death of the cell Syncytium formation (multinucleated cells) Malignant transformation (multi-step process) No morphologic changes

35 PATHOGENESIS OF VIRAL INFECTIONS The infected patient Transmission resp. secretions, saliva, blood, semen, faecal-oral Entry skin, resp. tract, GI tract, urogenital tract, conjunctiva Viral spread bloodsteam, lymphatics, along axons Cellular injury cytopathic effect, immune response Viral clearance antibodies, cellular immunity, interferons, cytokines Viral shedding necessary for transmission

36 PERSISTENT VIRAL INFECTIONS