Unit 3 Viruses and Human Diseases Dr Hengli Tang Ph D Virus An obligatory intracellular parasite that carry a nucleic acid genome enclosed by a protein coat o It s genome carry limited information o Can not survive outside the host cell o A virus lives a cushy life without doing much itself ICLICKER QUESTION Of the following which is the most serious threat to public health in your opinion B Influenza Avian Flu Viral Disease Ancient Records o Egyptian stone tablet 1500 B C showing Polio o When was virus discovered It was after the final defeat of the Spontaneous Generation theory and the acceptance of the germ theory in the late 1800 s D Ivanowsky A Mayer and M Beijerinck All essential to identifying the first viruses What does a virus look like o Viruses are SMALL A micrometer m 10 3mm 10 6mm A micrometer m 1 Micron A nanometer nm 10 3 m A nanometer nm 10 Angstroms o They come in different shapes Helical Derivations and combinations of Helical and Icosahedron Icosahedron ICLICKER QUESTION One micron equals E 10 000 o Small Some bigger than others o Too Small to be seen Microscopes needed FEI 4 800 000 16 feet tall 1 7 Tons Light Microscope Resolution Ability to distinguish two objects as separate entities Resolution 200 350 nm Uses light as a source of illumination Can see human cells and bacteria Can t see viruses Fluorescent Light Microscopy Time lapse video microscopy Movies of Cells Electron Microscopy A comparison with light microscopy 1 Uses electronic beams instead of lights 2 100 times higher resolution can see interior structures of the cells and structure of the viruses Transmitted and Scanning Electron Microscopy TEM examines the cross section of biological samples CryoEM Ultra low temperature and quick freezing to preserve the native unfixed structure of the virus EM Tomography CT Scan of viruses The sample is tilted the microscope stays stationary SEM scans the surface of biological structures o Virions Also called virus particles consist of RNA or DNA genome packaged within a protein coat and in some cases a lipid envelope Viruses come in all shapes but many are Icosahedrons o Viruses need to use minimal number of proteins to make the virion o Closed shells made of identical subunits can only have limited types of symmetry Tetrahedron Cube Icosahedron Viruses are everywhere o Viruses weigh 1000 times more than elephants 1031 32 viruses on Earth o Everyone in this room is infected with 2 3 Herpes viruses o We all carry retroviral elements in genome o Viruses are not all bad Sometimes a virus benefits an infected host Potential role in maintaining carbon and oxygen cycles of Tools for research and medicine atmosphere Family Flaviviridae Hepacivirus Hepatitis C Canine Genus Flavivirus Dengue West Nile Yellow Species Fever Hepatitis Retroviridae Pestivirus Lentivirus Bovine viral diarrhea virus HIV 1 HIV 2 SIV FIV Major scientific discoveries made by studying viruses o Vaccines protect from re infection o DNA not protein or sugar is the genetic material Bacteriophages also called phages for short are viruses that infect bacteria o Viral infections can cause cancer o Oncogenes good genes gone bad o Tumor suppressor genes guarding angels of our genome o Viruses can be modified to deliver medicine to treat genetic disease ICLICKER QUESTION A race car driver drove the first lap around the track at 100 mph how fast would he have to go for the second lap if he wants to achieve at the end of the second lap an average speed of 200 Viruses have families too o Family genus species What s in the name o Disease symptoms o Locations of discovery o Scientists who discovered the virus o Other mph for the two laps A 300 mph The life cycle of a virus o Overview 1 Bind to viral receptor 2 Entry and coating 3 Early Gene expression 4 Replication of viral genome 5 Late gene expression 6 Assembly of progeny virions 7 Viral release exit o Step 1 Entry Virus entry is a multistep process with the ultimate goal of delivering viral genome payload into the cells Virions binding to cell surface receptors A viral receptor is cell surface molecule likely a transmembrane protein A virus may need multiple receptors to enter a cell The ability of viruses to infect certain cells but not others are typically due to the fact that the only permissive cells display the right viral receptors This is called virus tropism Many viruses are species specific partially due to receptor differences o Membrane structure and hydrophobicity Transmembrane protein A protein that spans across the membrane lipid bilayer at least once The viral receptor is displayed on the cell surface for normal cell functions but hijacked by the virus to latch on to the cells o Identification of HIV receptors A cell surface molecule called CD4 is the primary receptor for HIV HIV only infects a subset of human T cells that express a cells surface molecule called CD4 HIV envelope protein binds to CD4 and blocking of this interaction prevents HIV entry HIV infection selectively depletes CD4 expressing T cells weakening the immune system However mouse cells expressing human CD4 molecules is still not permissive for HIV entry CD4 is necessary but not sufficient for entry o Identification of HIV receptors was possible because of contributions A young scientist in Bethesda MD at the National Institutes of from Health A brilliant but somewhat arrogant pioneer in HIV research A group of Nairobi sex workers who carried a black book of phone numbers of clients ICLICKER QUESTION Virus Tropism refers to C The fact the virus can only infect certain cell types but not others H5N1 Avian flu virus Named after two surface glycoproteins HA hemagglutinin and NA neuraminidase Normally infects but does not cause disease in aquatic birds Changes in HA which broaden receptor specificity and increase in receptor affinity cause concerns Becomes highly contagious and pathogenic in birds 1996 called highly pathogenic avian Gains ability to infect mammals including influenza HPAI humans 1997 Gains the ability to transmit in between mammals including humans Membrane penetration by viruses employs two basic strategies pore formation and membrane fusion Membrane pores at the cell surface Endocytosis cellular uptake of materials from extracellular Jail breaking from endosome low pH dependent membrane space fusion Low pH in the endosome triggers membrane pinching and fusion ICLICKER QUESTION Which of the following is a possible route of virus entry E Al of the Above
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