BSC1005 Unit 3 Prof Hengli Tang Viruses and Human Diseases Lecture 1 What is a Virus an obligatory intercellular parasite that carry a nucleic acid genome enclosed by a protein coat its genome carry limited information they do not have all of the information to carry itself forward to the next cell can not survive outside the host cell Why study viruses The Fear of our lives iclicker Of the following which is the most serious threat to public health in your opinion cold virus influenza avian flu a b c Ebola virus and hemorrhagic fever d carnival cruise Viral Diseases ancient records Egyptian stone tablet drew Polio diseases on it 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 1800s the origin of germ theory through the idea that something in the air will rot your food 3 scientists together worked for this Mayer Ivanowsky and Beijernick Viruses are small but compared to what A micrometer 10 3 mm A micrometer 1 micron A nanometer 10 3 um A nanometer 10 A iclicker One micron equals a 1 A b 10 A c 100 A d 1 000 A e 10 000 A Small some bigger than others Mimivirus are actually giant viruses some are too small to be seen Light microscope uses light as source of illumination can see human cells and bacteria can t see viruses 1 000 magnification resolution the ability to distinguish two objects as separate entities Fluorescent Light Microscopy green fluorescent cells are the ones infected with the virus time lapse video microscopy movies of cells Electron Microscopy A comparison with light microscopy 1 main difference is the resolution 2 uses electronic beams instead of lights 3 100 times higher resolution can see interior structures of the cells and structure of viruses can only look at dead specimen because of vacuum requirement complicated sample prep 4 5 Transmitted and Scanning EM electron microscopy TEM examines the cross section of biological studies SEM scans the surface of biological structures Specialized TEM techniques CryoEM ultra low temperature and quick freezing to preserve the native structure of the virus EM Tomography CT scan of viruses the sample is tilted the microscope scanner stays stationary Determining Virion Structure Virions also called virus particles consist of an RNA or DNA genome packaged within a protein coat and in some cases a lipid envelope EM images crystal structures x ray diffraction computation modeling Viruses come in all shapes but many are icosahedrons Viruses need to use minimal number of proteins to make the virion closed shells made of identical subunits can only have limited types of symmetry Viruses are everywhere viruses weigh 1000 times more than elephants 10 31 32 viruses on earth everyone in this room is infected with 2 3 herpes viruses we all carry retroviral elements in genome viruses that affect germ line cells over generations Viruses are not all bad sometimes a virus benefits an infected host potential role in maintaining carbon and oxygen cycles of atmosphere tools for research and medicine common flu common cold warts bad ones HIV ebola Major scientific discoveries made by studying viruses Vaccines protect from re infection DNA not protein or sugar is the genetic material o Bacteriophages also called phages for short are viruses that infect bacteria Viral infections can cause cancer Oncogenes good genes gone bad genes that cause cancer then they perform beyond their normal function that s when problems arrive and tumor suppressor genes guarding angels of our genome o Cancer cells are fast dividing Viruses can be modified to deliver medicine to treat genetic diseases the process of giving somebody a gene is mediated by viruses Viruses have families too family genus and species What s in a name disease symptoms location of discovery scientists who discovered the viros other iclicker a race car driver drove the first lap around the track at 100 mph how fast would he have to go to the second lap if he wants to achieve at the end of the second lap an average speed of 100 mph for the two laps a 300 mph b 400 mph c d cant be determined because not enough info given infinity Lecture 2 The Life Cycle of a Virus I entry A Bug s Life overview 1 binding to viral receptor 2 entry and uncoating 3 early gene expression 4 5 6 assembly of progeny virions form new copies of virus 7 viral release exit and then they travel around and find new cells to repeat this process replication of viral genome late gene expression Why are structural proteins typically made from late genes Structure proteins are used to assemble new viruses They have no use before the genome replication step Virus entry is a multistep process with the ultimate goal of delivering viral genome payload into the cells virions bind to cell surface receptors enveloped viruses and non enveloped viruses from enveloped viruses is goes to the membrane fusion at the cell surface and to the endocytosis which then membrane fusions in the endosome 1st step virus 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 a virus needs to find a specific cell to accept it virus tropism the ability of viruses to infect certain cells but not other are typically due to the fact that only the permissive cells display the right viral receptors many viruses are species specific partially due to receptor differences o Example HIV is species specific it can only affect Human T cells o WNV is carried in mosquitos and can affect humans animals etc Membrane structure and hydrophobicity Transmembrane protein a protein that span 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 the cells o These proteins on the cell membrane were there to perform their own function they just happen to be there when the virus tries to hijack it like water hate water o Hydrophilic o Hydrophobic Identification of HIV receptors part I a cell surface molecule called CD4 is the primary receptor of HIV o HIV only infects a subset of human T cells that express a cell surface molecule o HIV envelope protein bind to CD4 and blocking of this interaction prevent HIV o HIV infection selectively depletes CD34 expressing T cells weakening the called CD4 entry immune system However mouse cells expressing human CD4 molecule is not
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