Physiologic Development of VIRUSES. Dr A.Aziz Djamal MSc.DTM&H. SpMK(K)

D. IVANOWSKY. 1890: A Russian scientist proposed that tobacco mosaic disease was caused by a bacterium that was either too small to be trapped by a filter or that produced a filterable toxin. To remove bacteria, he filtered sap from infected leaves. Filtered sap still transmitted disease to healthy plants.

MARTINUS BEIJERINCK. 1897: A Dutch microbiologist proposed that the disease was caused by a reproducing particle much smaller and simpler than a bacterium. He ruled out the theory that a filterable toxin caused the disease by demonstrating that the infectious agent in filtered sap could reproduce.

Plants were sprayed with filtered sap from disease plants-----> sprayed plants developed tobacco mosaic disease----->sap from newly infected plants was used to infect others.

WENDELL. M. STANLEY. 1935:An American Biologist, from the Rockefeller Institute, crystallized the infectious particle now known as Tobacco Mosaic Virus(TMV). The purified virus precipitated in the form of crystals. He was able to show that viruses can be better regarded as chemical matter, than as living organisms.

Crystals retained the ability to infect healthy tissue. Subsequent determination of chemical nature of TMV: Protein in combo with nucleic, TMV were rods 300 nanometers long, TMV was RNA surrounded by protein coat.

GENERAL CHARACTERISTICS. Obligatory Intracellular Parasites. Protein coated fragments of DNA or RNA that have become detached from the genomes of cells. Because they cannot replicate on their own, they are not organisms. Viruses are generally host-specific.

They reproduce only within a certain host. Should be as many viruses as there are kinds of organisms.

VIRUS-HOST RANGE. The host range of a virus is the spectrum of host cells the virus can infect. Some viruses have broad host ranges which may include several species(e.g. swine flu and rabies). Some viruses have host ranges so narrow that they can: infect only one species(e.g. phages of E.coli

Infect only a single tissue type of one species(e.g. human cold virus infects only cells of the URT; AIDS virus binds only to specific receptors on certain white blood cells.

VIRAL SIZE. In the 1950’s, TMV and other viruses were finally observed with electron microscopes. Smallest = 17 nanometers in diameter. Largest = 1000 nanometers(1 micrometer) in greatest dimension. Few are barely visible at light microscope level. Most are visible only via EM.

VIRAL STRUCTURE. The virus or virion, is just nucleic acid enclosed by a protein coat, it’s a complete, fully developed infectious viral particle that is a vehicle of transmission from one host to another. Viruses are classified by differences in the structures of these coats.

NUCLEIC ACID- VIRAL GENOMES. Depending on the virus, viral genomes: May be double-stranded DNA, single- stranded DNA, double-stranded RNA or single-stranded RNA. Are organized as single nucleic acid molecules that are either linear or circular. May have as few as four genes or as many as several hundred.

CAPSID AND ENVELOPE. Capsid: Protein coat that encloses the viral genome. It’s structure may be rod-shaped, polyhedral or complex. Composed of many capsomeres: protein subunits made from only one or a few types of protein.

ENVELOPE. Membrane that cloaks some viral capsid: Helps viruses infect their host. Derived from host cell membrane which is usually virus-modified and contains proteins and glycoproteins of viral origin.

GENERAL MORPHOLOGY. Helical viruses. Polyhedral viruses. Enveloped viruses. Complex viruses.

HELICAL VIRUSES. Resemble long rods. Maybe rigid or flexible. Viral Genome found inside a hollow cylindrical capsid. E.G.: Ebola virus and Rabies virus.

POLYHEDRAL VIRUSES. Many-sided Capsid is in the shape of icosahedron( a polyhedral with 20 triangular faces). E.G.: Adenovirus, and poliovirus.

ENVELOPED VIRUSES. Roughly spherical. Enveloped-helical or enveloped polyhedral viruses. Enveloped helical = Influenzae virus. Enveloped polyhedral = Herpes simplex virus.

COMPLEX VIRUSES. Bacteriophage. Capsid(head) is polyhedral, tail sheath is helical. Tail fibers, plate and pin.

TAXONOMY OF VIRUSES. Viruses are not organisms and are not classified in the kingdoms of life. Regarded as self-replicating portions of the genomes of organisms. In comparison to living things, vruses are acellular(not cells and do not consist of cells), do not metabolize energy, no photosynthesis, cell respiration or ferment.

Viruses are cell parasites as they infect organisms at all taxonomic levels. Oldest classification based on symptoms. ICTV group vruses into families, based on: Nucleic acid type, strategy for replication, and morphology. E.G.: Family= ends with viridae. Genus= virus.

ISOLATION, CULTIVATION, AND IDENTIFICATION. Cannot replicate outside a living cell: poses problem with detection, ID, and cultivation. Bacteriophages are easily grown on bacterial cultures. This is the reason why so much of what is known of viral multiplication has come from from bacteriophage.

GROWING VRUSES IN THE LAB. Plaque method: Bacteriophages. Living animals: Animal viruses. Embryonated eggs: Animal viruses. Cell cultures: Animal viruses (CPE). Primary cell lines, Diploid cell lines, and continuous cell lines.

VIRAL MULTIPLICATION. Viruses are nonliving particles that reproduce only inside specific host cells. Exhibit many patterns of viral life cycle, but they generally include: Coopting host cell’s resources to: Manufacture capsid protein, Assemble newly produced viral nucleic acid and capsomeres.

Several mechanisms used to infect host cells with viral DNA. For example, T-even phages use an elaborate tailpiece to inject DNA into the host cell. Pinocytosis. Fusion with cell membrane

Once the viral genome is inside its host cell, it commandeers the host’s resources and reprograms the cell to copy the viral genes and manufacture capsid protein.

Three possible patterns of viral genome replication: 1. DNA---->DNA: If viral DNA is double- stranded, DNA replication resembles that of cellular DNA, and the virus uses DNA polymerase produced by the host.

2. RNA----->RNA: Since host cells lack the enzyme to copy RNA, most RNA viruses contain a gene that codes for RNA replicase RNA replicase is an enzyme that uses viral RNA as a template to produce complementary RNA.

3. RNA----->DNA----->RNA: Some RNA viruses encode reverse transcriptase, an enzyme that transcribes DNA from an RNA template.

MULTIPLICATION OF BACTERIOPHAGES. Studies on lambda phage of E. coli showed that double-stranded DNA viruses reproduce by two alternative mechanisms: The lytic cycle and the lysogenic cycle.

LYTIC AND LYSOGENIC CYCLES. Lytic cycle: Results in the death or lysis of the host cell. Bacteriophage takes over the machinery of the cell, so viral replication and release occur. Lysogenic cycle: Involves the incorporation of the viral genome into the host cell genome. Phage becomes a prophage, integrated into the host genome.

Virulent bacteriophage reproduce by a lytic replication cycle= that lyse their host cells. Later, the phage may reenter the lytic cycle and replicate itself. Temperate viruses= integrate and remain latent.

THE LYTIC CYCE. Attachment. Penetration. Biosynthesis. Maturation /Assembly. Release.

THE LYTIC CYCLE.

THE LYSOGENIC CYCLE. Lysogeny. Prophage. Phage conversion. Specilized transduction.

THE LYSOGENIC CYCLE.

MULTIPLICATION OF ANIMAL VIRUSES. Attachment. Penetration. Uncoating. Biosynthesis of DNA viruses. Biosynthesis of RNA viruses. Maturation/Assembly and Release.

DNA-CONTAINING VIRAL MULTIPLICATION.

RNA-CONTAINING VIRAL MULTIPLICATION.

RNA VIRAL MULTIPLICATION CONTD.

VIRUSES AND CANCER. Oncogenes. Oncogenic viruses. Contact Inhibition. Tumor-specific transplantation antigen (TSTA ).

LATENT VIRAL INFECTIONS. Latent Infection: Herpes simplex. Chicken pox (varicella). Shingles(zoster).

PERSISTENT VIRAL INFECTIONS. Persistent viral infections: Encephalitis called subacute sclerosing panencephalitis(SSPE).

PRIONS. Proteinaceous infectious particle that lacks nucleic acid. Nine animal diseases fall into this category. All nine are neurological diseases called spongiform encephalopathies. These diseases run in families, which indicates a possible genetic cause

Not Purely Inherited. However, The diseases cannot be purely inherited because mad cow disease arose from feeding scrapie-infected sheep meat to cattle, and the new (bovine) variant was transmitted to humans who ate undercooked beef from infected cattle.

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