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VIRUSES What are Viruses? • A virus is a non-cellular particle made up of genetic material and protein that can invade living cells. • The smallest biological particle that is capable of causing diseases in living organisms A Virus Has Two Essential Features • A Nucleic Acid – DNA or – RNA – But not both • A Capsid – a protein coat surrounding the nucleic acid. Viruses with RNA are called retroviruses. What are Viruses? A virus is an infectious agent made up of nucleic acid (DNA or RNA) wrapped in a protein coat called a capsid. Viruses have no nucleus, no organelles, no cytoplasm or cell membrane. This is why it does not belong to any kingdom. vs Not Considered Living • A virus is not a bacteria, fungus, protist, plant or animal. It needs a host! • They can not carry out cellular functions. • A virus can not replicate without infecting cells and then using the organelles and enzymes of the cells of the host. Viruses are parasites — an organism that depends entirely upon another living organism for its existence in such a way that it harms that organism. Who do viruses infect? Viruses usually infect a specific host including: • Viruses infect Bacteria – These viruses are called bacteriophages • Viruses infect Plants – One example is the Tobacco Mosaic Virus • Viruses infect Animals – One example is the common cold Bacteriophage—viruses that infect bacteria Capsid (protein coat) – inside contains either RNA or DNA Flu (influenza), HIV DNA or RNA Surface Marker Capsid (protein coat) Acute Virus Infection Amount of virus Symptoms Virus Time Why are some viruses harmful? When your cells make viruses instead of operating normally, you get sick Virus invades cell Virus forces cell to make copies of virus Eventually so many copies are made, the cell explodes, releasing all of the new viruses Replication Phases I, II, III - Viruses enter cell - Phase I Attachment to cell membrane Penetration inside cell Losing virus protein coat IV - Replication - Tricks cell into making more viral DNA Tricks cell into making viral protein coat Phase II V - Release - - Assembly of virus DNA and protein coat into whole new viruses Leaving the cell Phase III Phase IV Phase V Bacteriophage Replication Bacterial cell wall Bacterial chromosome Capsid DNA Capsid 1 Sheath Attachment: Phage attaches to host cell. Tail fiber Base plate Pin Cell wall Tail Plasma membrane 2 Penetration: Phage pnetrates host cell and injects its DNA. Sheath contracted Tail core 3 Merozoites released into bloodsteam from liver may infect new red blood cells 11 Bacteriophage Replication Tail DNA 4 Maturation: Viral components are assembled into virions. Capsid 5 Release: Host cell lyses and new virions are released. Tail fibers 12 Examples of some viral diseases: DISEASE VIRUSES AIDS HIV Wart Herpes Simplex Virus Flu Influenza Measles Morbillivirus . Cancer Hepatitis B Viral Shapes Viruses come in a variety of shapes •Some may be helical shape like the Ebola virus •Some may be polyhedral shapes like the influenza virus •Others have more complex shapes like bacteriophages Helical Viruses copyright cmassengale 15 Polyhedral Viruses copyright cmassengale 16 Complex Viruses copyright cmassengale 17 Where viruses have come from? 4 Billion Years Ago The surface of the planet is just cooling and beginning to harden into a crust. Rain forms pools containing many organic molecules and the first simple life forms appear. The first viruses also appear. It is not clear where they have come from. Where viruses have come from? •Regressive evolution - maybe these early viruses are degenerate lifeforms which have lost many functions that other organisms possess and have only retained the genetic information essential to their parasitic way of life. •Cellular origins - perhaps they are sub-cellular, functional assemblies of macromolecules which have escaped their origins inside primitive cells. •Independent entities - or maybe they just evolved from the selfreplicating molecules believed to have existed in the primitive prebiotic 'RNA world' along a parallel course to cellular organisms. 100 Million Years Ago. The Cretaceous Period. Dinosaurs roam the earth. The supercontinent Pangaea has begun to break up, but the continents have still not drifted into their present positions. The climate is much hotter and drier than today. Way out in space, a big meteorite is tumbling towards Earth ... The Year 3700 BC The first written record of a virus infection consists of a hieroglyph from Memphis, the capital of ancient Egypt, drawn in approximately 3700 BC, which depicts a temple priest called Ruma showing typical clinical signs of paralytic poliomyelitis. Poliomyelitis (Polio) is a viral disease which may affect the spinal cord causing muscle weakness and paralysis. The Year 1193 BC The Pharaoh Siptah rules Egypt from 1200-1193 BC when he dies suddenly at the age of about 20. His mummified body lays undisturbed in his tomb in the Valley of the Kings until 1905 when the tomb was excavated. The mummy shows that his left leg was withered and his foot was rigidly extended like a horse's hoof - classic paralytic poliomyelitis The Year 1143 BC Ramesses V's preserved mummy shows that he died of smallpox at about the age of 35 in 1143 BC. The lesions on the face of the mummy are very similar to those of more recent patients. Smallpox is a disease caused by the Variola major virus. Some experts say that over the centuries it has killed more people than all other infectious diseases combined. The Year 1520 Smallpox, which had reached Europe from the East in 710 A.D., was transferred to the Americas by Hernando Cortez. 3,500,000 Aztecs died in the next 2 years - effectively the end of the Aztec empire. The Year 1796 On 14th May 1796, Edward Jenner vaccinated an 8 year old boy, James Phipps, with material from a cowpox lesion on the hand of a milkmaid, Sarah Nelmes. James, who had never had smallpox, developed a small lesion at the site of vaccination which healed in 2 weeks. On 1st July 1796, Jenner challenged the boy by deliberately inoculating him with material from a real case of smallpox! Deadly viruses are said to be virulent Smallpox has been eradicated in the world today The Year 1886 John Buist stained lymph from skin lesions of a smallpox patient and saw "elementary bodies" which he thought were the spores of micrococci. These were in fact smallpox virus particles - just large enough to see with the light microscope. •Viruses are smaller than the smallest cell, measured in nanometers •Most of the viruses couldn’t be seen until the electron microscope was invented in the 20th century Size of Viruses copyright cmassengale 27 The Year 1892 Dmitri Iwanowski, a Russian botanist, presents a paper to the St. Petersburg Academy of Science which shows that extracts from diseased tobacco plants can transmit disease to other plants after passage through ceramic filters fine enough to retain the smallest known bacteria. This is generally recognised as the beginning of Virology. Unfortunately, neither Iwanowski nor the scientific community fully realize the significance of these results. Walter Reed (1851-1902) During the Spanish-American War and subsequent building of the Panama Canal, American deaths due to yellow fever were colossal. The disease also appeared to be spreading slowly northward into the continental United States. Through experimental transmission to mice, in 1900 Walter Reed demonstrated that yellow fever was caused by a virus, spread by mosquitoes. Karl Landsteiner (1868-1943) Karl Landsteiner (1868-1943) and Erwin Popper proved that poliomyelitis was caused by a virus. Landsteiner and Popper were the first to prove that viruses could infect humans as well as animals. Francis Peyton Rous (1879-1970) Francis Peyton Rous (1879-1970) demonstrated that a virus (Rous sarcoma virus) can cause cancer in chickens. (For this work, he was eventually awarded the Nobel Prize, in 1966. Rous is the first person to show that a virus could cause cancer in animals. Treatment and Prevention of Virus Infections • Antivirals • Vaccines and immunisation Antiviral Targets • Attachment/Entry • Nucleic acid replication • Virus protein processing • Virus maturation Vaccines • An attenuated virus is a weakened, less vigorous virus • “Attenuate" refers to procedures that weaken an agent of disease (heating) • A vaccine against a viral disease can be made from an attenuated, less virulent strain of the virus • Attenuated virus is capable of stimulating an immune response and creating immunity, but not causing illness copyright cmassengale 34 Incidence of Poliomyelitis A B Number of cases (in thousands) 40 Poliovirus vaccines A: Salk – killed inactivated vaccine. B: Sabin – live attenuated vaccine 30 20 10 0 1950 1960 1970 1980 Problems with Antivirals • Identification of virus-specific target. • Generation of resistant variants. Weapons • The ability of viruses to cause devastating epidemics has led to the concern that viruses could be weaponised for biological warfare. • Further concern was raised by the successful recreation of the infamous 1918 influenza virus in a laboratory. • The smallpox virus devastated numerous societies throughout history before its eradication. • There are only two centers in the world that are authorized by the WHO to keep stocks of smallpox virus: the Vector Institute in Russia and the Centers for Disease Control and Prevention in the United States. • However as the vaccine for smallpox is no longer used routinely in any country, much of the modern human population has no established resistance to smallpox.