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Transcript
• Virology – Study of viruses The word virus comes from a Latin word meaning poison. • “Humans have long been familiar with the ravages of viruses, if not the creatures themselves. Dried pustules on the mummified face of Ramses V testify to the fact smallpox killed even in mighty Egypt 3,000 years ago.” –Time Magazine Nov 3, 1986 Edward Jenner • (1798) He noticed that farmhands who contracted cowpox, a mild disease related to smallpox, did not develop the more deadly disease. Jenner inoculated a boy with material from a milkmaid’s cowpox sore, then demonstrated, that the boy and developed immunity to smallpox. This may be considered the first vaccine. Louis Pasteur • (Late 1800s) He developed a vaccine of a weakened virus to protect a young boy against rabies. Dmitri Ivanovski • (1892) –pinpointed the cause of tobacco mosaic disease to the juice extracted from infected tobacco plants. Martinus Beijerinck • (1897) – He determined that tiny particles in the juice from the Tobacco leaves caused the disease. He names these particles viruses. Dr. Wendall Stanley (1935) • He was the first to isolate & crystallize a virus (TMV). Since a virus can be crystallized, it became clear that they were not really living things. • He removed fluid from approximately one ton of infected and diseased tobacco leaves. He obtained one teaspoon of crystal substance. (He shared the Nobel prize with for his work) The invention of the electron microscope allowed biologists to see viruses, which are too small to be seen by light microscopes. Viruses don’t share characteristics of living organisms. Are they Alive? They have no nucleus, cytoplasm or organelle. They need no nourishment. They have no cell membrane. They have no metabolic processes. They have no means of locomotion. They do not respond to their environment (except when they come in contact with the correct receptor site on a host cell.) Virus Characteristics: • A typical virus is composed of a core of either DNA or RNA surrounded by a protein coat called a capsid. (usually about 95% of the total mass) • Some capsids are surrounded by a membrane envelope. These are referred to as enveloped viruses. The envelope allows the virus to attach to their host cell. • Viruses may have a few genes or as many as a thousand. Viral Shape: • Virus shape may be determined by its capsid, or its nucleic acid. Common viral shapes are: • Helix-Shape (rod)– Tobacco Mosaic • Icosohedron – 20 triangular faces Cubic Symmetry • Example: Adenovirus – a respiratory tract virus. It has spikes to attach to host cell. It has 252 “capsomeres” and reproduces in nucleus of the host cell. Bacteriophage: Virus that infects bacterial cells. “Phage” HIV -Structure (Human Immunodeficiency Virus) • HIV is a retrovirus, which means that it carries RNA instead of DNA, and has an enzyme called Reverse Transcriptase. This enzyme uses the RNA as a template to make DNA. The viral DNA becomes incorporated in the host cell. • The virus, like others (such as chicken pox or influenza) is surrounded by an envelope of mostly lipids. On the surface are projections made of glycoproteins, which are protein containing sugar chains that the virus used to attach to its host cell. • This eventually destroys the cell, weakening the immune system. • A person gets sick from opportunistic infections that a normal immune system could stop. (These may include cancer, fungal infection, bacterial infections etc.). VACCINE (from the word “vaccinus” Latin “pertaining to cows.) Definition: • A preparation of pathogens or other materials that stimulates the body’s immune system to provide protection against that pathogen • Attenuated – viruses that have been genetically altered so that they are incapable of causing disease under normal circumstances. VIROIDS AND PRIONS: • Viroids are the smallest known diseasecausing agents that are able to replicate. It consists of a short, single strand of RNA and has no capsid. They cause disease in plants. • Prions – normal proteins called prions can become abnormal forms of proteins that clump together inside a cell, perhaps by blocking the cells “molecular traffic.” (commonly about 250 amino acids long). They cause other prions in the brain to become abnormal. Prions are linked to brain diseases in humans and animals. • Kuru – Anxiety yields to trembling, loss of coordination and death in 16 months. (It was once contracted by cannibals in New Guinea from eating infected human brains) • Mad Cow Disease is a Prion disease that affects cow brains. Creutzfeldt-Jakob (CJD) • Human form of the Bovine spongiform encephalopathy (BSE) AKA “Mad Cow Disease” Begins with depression & memory problems. In 4-6 months it progresses to dementia, uncontrollable jerking of muscles and finally death. • The first known prion disease was scrapie, which has infected sheep for many years. In the 1980s, Britain had an outbreak of bovine spongiform encephalopathy, better known as mad cow disease, which spread to Europe and other areas. Two cows have been found with the illness in the United States. • The human form of the illness is called variant Creutzfeld-Jakob disease and is believed to have originated from eating infected beef. It has killed about 180 people worldwide. Symptoms can take years to develop. • ALSO – “Fatal Insomina” Prion disease in humans: Progressive insomnia leads to panic attacks, phobias, hallucinations and finally dementia. Death occurs within 18 months. ANTIVIRAL APPROACHS: • Acyclovir – used against herpes simplex and Chicken pox (Varicella) • AZT – inhibits reverse transcriptase in HIV • Protease Inhibitors – interfere with the synthesis of viral capsids during viral replication. • ANTIBIOTICS ARE NOT USEFUL AGAINST VIRUSES! • Virus particles have been used to insert genes into cells during recombinant DNA activities. A bacteriophage that infects E. coli is used. The virus’ own genes are removed from the capsid and replaced by new gene --- the gene that codes for the human protein. Reproduction by the Lytic Cycle • During the Lytic Cycle a virus invades the host cell, produces new viruses, destroys the host cells , and releases newly formed viruses. Viruses that undergo the lytic cycle are considered virulent because they can cause disease. • 1) Attachment – the bacteriophage attaches its tail fibers to the bacterial cell receptor site. • 2) Entry – The virus releases an enzyme that weakens the cell wall of the host cell. It then injects its DNA into the host cell. (It leaves the capsid outside the host cell.) • 3) Replication – The virus takes control of the bacterial cell’s protein synthesizing machinery, transcribing mRNA from viral DNA. Viral proteins are formed as well a new viral capsids. Viral genes are replicated. • 4) Assembly – The replicated viral genes are enclosed within newly created virus capsids. (The assembly of new virus particles usually occurs in the cytoplasm of the host cell, but it may also take in the eukaryotic cell nucleus.) • 5) Release (Lysis) – Enzymes are produced that cause the host cell to disintegrate, releasing the new bacteriophages. • In enveloped viruses, the virus leaves with a piece of the membrane surrounding the capsid. This becomes the viral envelope. The Lysogenic Cycle • A virus that replicates through the lysogenic cycle does not kill the host cell immediately. It may stay in the host for days, months or even years. • The virus in this cycle is called a temperate virus. The virus DNA is incorporated in the cell DNA, at a site in the host cell genome, is called a prophage. (provirus) The prophage is replicated with the cell DNA and is passed to daughter cells. • When the prophage becomes virulent, (reproduces & can cause disease) due to certain chemicals or radiation, it enters the lytic cycle, proceeding with replication and destroys the host cell. Chickenpox and Shingles • Caused by varicella-zoster herpes virus • Virus multiplies in lungs and travels to blood vessels in the skin. (symptoms: fever & skin rash) • It spreads through air or direct contact • It can stay in nerve cells as a provirus. • It can later cause a disease known as shingles (causes a painful rash)