Virology

Historical Timeline
1500 B.C.: Polio in Egypt 1200 B.C.: Smallpox in Egypt 11th century: Variolation practised in Asia and Africa: the deliberate infection of smallpox virus.

Historical Timeline
1677 Observed "little animals" (Antony Leeuwenhoek) 1796 First scientific Small pox vaccination (Edward Jenner) 1850 Advocated washing hands to stop the spread of disease (Ignaz Semmelweis)

Historical Timeline
1861 Disproved spontaneous generation (Louis Pasteur) 1862 Supported Germ Theory of Disease (Louis Pasteur) 1867 Practiced antiseptic surgery (Joseph Lister)

Historical Timeline
1876 First proof of Germ Theory of Disease with B. anthracis discovery (Robert Koch) 1881 Growth of Bacteria on solid media (Robert Koch) 1882 Outlined Kochs postulates (Robert Koch)

Historical Timeline
1882:Developed acid-fast Stain (Paul Ehrlich) 1884:Developed Gram Stain (Christian Gram) 1885:First Rabies vaccination (Louis Pasteur)

Historical Timeline
1887:Invented Petri Dish (R.J. Petri) 1892:Discovered viruses (Dmitri Iosifovich Ivanovski) 1899:Recognized viral dependence on cells for reproduction (Martinus Beijerinck)

Historical Timeline
1900:Proved mosquitoes carried the yellow fever agent (Walter Reed) 1910:Discovered cure for syphilis (Paul Ehrlich) 1911: Francis Peyton Rous in 1911 described an oncovirus in chickens. 1911: Frederick Twort recognized the existence of viruses that infect bacteria. 1928:Discovered Penicillin (Alexander Fleming)

Historical Timeline
1935: Wendell Stanley achieved the crystallization of the tobacco mosaic virus for electron microscopy and showed that it remains active even after crystallization. 1937: Max Delbruck described the basic life cycle of a virus.

Historical Timeline
1937: Max Theiler grew the Yellow Fever virus in chicken eggs and produced a vaccine from an attenuated virus strain. 1952: Hershey-Chase experiment showed that only DNA and not protein enters a bacterial cell upon infection with bacteriophage T2.

Historical Timeline
1955: Rosalind Franklin proposed the full structure of the tobacco mosaic virus. 1963: Hepatitis B virus discovered by Baruch Blumberg. 1965: Howard Temin described the first retrovirus. 1976: First recorded outbreak of Ebola hemorrhagic fever.

Historical Timeline
1977: Developed a method to sequence DNA (W. Gilbert & F. Sanger) 1982: Stanley Prusiner discovered prions and showed that they cause scrapie. 1983: Polymerase Chain Reaction invented (Kary Mullis) 1985: Harald zur Hausen showed that two strains of the Human Papillomavirus (HPV) cause most cases of cervical cancer.

Historical Timeline
1995:First microbial genomic sequence published (H. influenzae) 2002: Poliovirus was synthetically assembled in the laboratory. 2003: Bacteriophage Phi X 174 was synthetically assembled in the laboratory. 2004: Giant mimivirus was sequenced. 2006: Two vaccines protecting against the two cancer causing strains of the HPV were released.

Virology
A virus is an obligate intracellular parasite containing genetic material surrounded by protein Virus particles can only be observed by an electron microscope

Introduction to Virology
The classification of viruses is based on the type of nucleic acid contained within
RNA viruses---also known as a retrovirus DNA viruses

Virus
Latin for slimy liquid or poison Virus particle or virion - Infectious agent composed of nucleic acid (RNA or DNA), a protein shell (capsid) and, in some cases, a lipid envelope Capsid - Protein coat that surrounds the viral nucleic acid - Composed of repeating subunits called capsomeresHave either icosahedral or helical symmetry

Virus
Nucleocapsid- Complete protein-nucleic acid complex Satellite or defective viruses - Viruses which require a second (helper) virus for replication Example: hepatitis delta virus requires hepatitis B Viroids - Small, autonomously replicating molecules - Single stranded circular RNA, 240-375 residues in length - Plant pathogens

Viral Size Range

Ultramicroscopic smallest infectious agents 2,000 bacterial viruses could fit into an average bacterial cell 50 million poliovirus could be accommodated in the human cell Animal viruses range in size from the small parvoviruses1 (around 20 nm [0.02 m] in diameter) to poxviruses2 that are as large as small bacteria (up to 450 nm [0.4 m] in length) Electron microscopy is used together with negative staining Negative staining uses very thin layers of an opaque salt to outline the shape of the virus against a dark background and to enhance textural features on the viral surface. for internal staining we shadowcasting technique, which attaches a virus preparation to a surface and showers it with a dense metallic vapor directed from a certain angle

Virus Classification
Older based on - Host, target organ or vector Modern based on - Type of viral nucleic acid RNA or DNA Single stranded (SS) or double stranded (DS) Replication strategy - Capsid symmety Icosahedral or helical - Presence or absence of lipid envelope Governed by International Committee on Taxonomy of Viruses

Virus Classification
2000 the International Committee on the Taxonomy of Viruses issued their latest report on the classification of viruses. They listed 3 orders, 63 families, and 263 genera of viruses.

Virus Components
Viral components 1. Nucleic acid constitute the genome/genetic information; may be single stranded or double stranded - It may be linear, circular or segmented 2. Capsid protein coat that enclosed that nucleic acid; of one or more protein specific to virus; protects genome and determines viral shape; helps virus attach to host cell;may be helical or icosahedral Capsomeres- multiple proteins subunits of a capsid 3. Envelope bilayer membrane outside the capsid; acquired only after they bud through hosts cell membrane; with viral glycoproteins that are spikelike or spikes which allow viruses to attach to specific receptors or host cells surface and to allow fusion of viral and cell membrane.

Capsid Symmetry

Capsid Symmetry

Icosahedral
An icosahedron is a Platonic solid with twenty faces and 5:3:2 rotational symmetry . There are six five-fold axes of symmetry through which the icosahedron can be rotated passing through the vertices, ten 3-fold axes of symmetry passing though each face and fifteen two-fold axes of symmetry passing through the edges There are twelve corners or vertices and 5-fold symmetry around vertices. The capsid shell is made of repeating subunits of viral protein All faces of the icosahedron are identical.

Helical
Protein subunits can interact with each other and with the nucleic acid to form a coiled, ribbon like structure. The best studied virus with helical symmetry is the nonenveloped plant virus, tobacco mosaic virus The helical nature of this virus is quite clear in negative staining electron micrographs since the virus forms a rigid rod-like structure. In enveloped, helically symmetrical viruses the capsid is more flexible (and longer) and appears in negative stains rather like a telephone cord

Helical

FIVE BASIC STRUCTURAL FORMS OF VIRUSES IN NATURE

Naked icosahedral e.g. poliovirus, adenovirus, hepatitis A virus Naked helical e.g. tobacco mosaic virus. So far no human viruses with this structure are known Enveloped icosahedral e.g. herpes virus, yellow fever virus, rubella virus Enveloped helical e.g. rabies virus, influenza virus, parainfluenza virus, mumps virus, measles virus Complex e.g. poxvirus

 1. Polio virus 2. flexible taile bacteriophage

With a helical nucleocapsid: (3) mumps virus (4) rhabdovirus With an icosahedral nucleocapsid: (5) herpesvirus (6) HIV (AIDS)

C. Naked viruses: Helical capsid: (7) plum poxvirus Icosahedral capsid: (8) poliovirus (9) papillomavirus

Viral envelope
released from the host cell, they take with them a bit of its membrane system in the form of an envelope In the envelope, some or all of the regular membrane proteins are replaced with special viral proteins Some proteins form a binding layer between the envelope and capsid of the virus, and glycoproteins remain exposed These spikes or peplomers are essential for attachement. Envelope is more supple than the capsid, enveloped viruses are pleomorphic and range from spherical to filamentous in shape

Function of Capsid/Envelope
indispensable to viral function because it protects the nucleic acid from the effects of various enzymes and chemicals when the virus is outside the host cell Capsids and envelopes are also responsible for helping to introduce the viral DNA or RNA into a suitable host cell, first by binding to the cell surface and then by assisting in penetration of the viral nucleic acid parts of viral capsids and envelopes stimulate the immune system to produce antibodies that can neutralize viruses and protect the hosts cells against future infections

Nucleic Acids:At the Core of a Virus

viruses contain either DNA or RNA but not both viruses must pack into a tiny space all of the genes necessary to instruct the host cell to make new viruses, the number of viral genes is quite small compared with that of a cell Viruses possess only the genes needed to invade host cells and redirect their activity. DNA viruses can have single-stranded (ss) or doublestranded (ds) DNA; the dsDNA can be arranged linearly or in ds circles. RNA viruses can be double-stranded but are more often single-stranded.

Nucleic Acids:At the Core of a Virus

all proteins are made by translating the nucleic acid code on a single strand of RNA into an amino acid sequence Single-stranded RNA genomes that are ready for immediate translation into proteins are called positive-sense RNA Other RNA genomes have to be converted into the proper form to be made into proteins, and these are called negativesense RNA RNA genomes may also be segmented, meaning that the individual genes exist on separate pieces of RNA An RNA virus with some unusual features is a retrovirus, one of the few virus types that can change its nucleic acid from RNA to DNA

Nucleic Acids:At the Core of a Virus

Viruses are genetic parasites

they must carry genes for synthesizing the viral capsid and genetic material, for regulating the actions of the host, and for packaging the mature virus

Complex Viruses:Atypical Viruses

poxviruses (including the agent of smallpox) are very large DNA viruses that lack a typical capsid and are covered by a dense layer of lipoproteins and coarse fibrils on their outer surface bacteriophages, have a polyhedral capsid head as well as a helical tail and fibers for attachment to the host cell. Their mode of multiplication is covered in section

Vaccinia virus

UNCONVENTIONAL AGENTS
There are also the 'unconventional agents' sometimes known as 'unconventional viruses' or 'atypical viruses' - Up to now, the main kinds that have been studied are viroids and prions.

UNCONVENTIONAL AGENTS
VIROIDS - Viroids contain RNA only. - They are small (less than 400 nucleotides), single stranded, circular RNAs. - The RNAs are not packaged, do not appear to code for any proteins, and so far have only been shown to be associated with plant disease. However, there are some suggestions that somewhat similar agents may possibly be involved in some human diseases.

UNCONVENTIONAL AGENTS
PRIONS - Prions contain protein only. - They are small, proteinaceous particles and there is controversy as to whether they contain any nucleic acid, but if there is any, there is very little, and almost certainly not enough to code for protein: - Examples of prion-caused human diseases are Kuru, Creutzfeldt-Jakob disease and Gerstmann-Straussler syndrome. Prions also cause scrapie in sheep.

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