BSC 1005 Viruses Human Disease Study Guide Chapter 1 Overview The tobacco mosaic disease began the studies of viruses o Tobacco mosaic virus TMV is the transmissible agents are responsible for the tobacco mosaic virus The first isolated animal virus was in 1898 The first human virus was recognized at the turn of the 20th century Viral infections of plants lead to the loss of crop yield in the range of tons of billions of dollars each year NOT all viral infections manifest a negative effect in the host Viruses can tell us how cells work o Many biological concepts come from studying viruses New viruses are still being discovered Virus an obligatory intercellular parasite that carries a nucleic acid genome enclosed by a protein coat Enveloped viruses lipid membrane outside the coat A virus is NOT a cell o Viral genome carries limited information o A virus cannot survive long outside the host cell because it lacks the ability for metabolism o Virus does not do much itself Viruses are small and need a microscope to visualize them o Light microscope uses photons o Electron microscope uses electrons Electron microscope needs a vacuum which prevents it from imaging living samples o Can only see dead specimen Uses electronic beams Light microscope is used to trace real time changes in the host cell caused by an infection o Cannot see viruses Sources of illumination of light and electron microscopes are different There are different types of EM techniques o TEM examines the cross section of biological samples o SEM scans the surface of biological structures o CryoEM ultra low temperature and quick freezing to preserve the structure o EM Tomography CT scan of viruses except in this case sample is titled the microscope stays stationary Physical entity of a virus is called a virus particle also known as a virion Virion virus particles A virion refers to a physical particle where as a virus is a more general term o Virion consists of a nucleic acid RNA or DNA genome packaged within a protein coat Virions can be spherical rod like filamentous or all of them o Knowledge of these virions help design effective vaccinations A cold sore that many humans receive is the herpes virus infection Retro transposons viral genetic information carried in cells Names of viruses ending in o viridae refers to virus families o virus represent viral genera Virus can be classified by the nature and the organization of their genetic Resolution of a microscope ability to distinguish two objects as separate materials entities Bacteriophages viruses that infect bacterial cells A micron 1 micron 1 micrometer Bacterial and eukaryotic cells are in this range 10 100 micrometers A filter with 0 2 micron sized pores will effectively remove bacterial contamination by trapping them in the filter A nanometer nm Viruses are in this range 20 100 nm is the typical range of diameters for viruses The same filter mentioned above will not remove most viruses Angstrom A Molecules are in this range A nanometer nm 10 angstrom Chapter 2 Virus Entry A cell surface Viruses depend on their host cells for survival and most events occur inside a Virus binding virus finding the right target cell and latching onto its The step after virus binding is followed by the internalization step of the virus or part of the virus o This step requires penetration of the cell membrane The penetrations involve either direct penetration or fusion penetration Viral receptors a cell surface molecule that is bound by a virus to mediate its entry into host cells A virus may need multiple receptors to enter a cell o The phenomenon that viruses are capable of infecting certain cell types but not others This is called tropism Viruses are also species specific only infect one species due to receptor Species specific receptor specific differences Receptors are host cells molecules that have normal functions for the cells but are hijacked by the virus to gain entry during an infection event Receptors are host proteins with normal functions HIV uses two distinct protein receptors for its entry o Primary receptor CD4 Expressed on a subset of white blood cells called T cells HIV can only infect these immune cells o Secondary receptor CCR5 Belongs to the family protein called chemokine receptors which normally function in chemical sensing and cell to cell communications FDA approved CCR5 inhibitor for treatment of HIV infection in 2007 Contacting surfaces of two proteins to interact requires them to be compatible in shape as well as chemical properties such as charge and hydrophobicity o Hydrophobicity is the level of water repulsion A change in the surface structure can broaden the tissue or host range of the virus and result in serious consequences Crossing the Membrane Barrier A virus has to transport the payload viral genome across the membrane of the cell to then go inside the cell o The process primarily happens with one of the two main mechanisms o Pore formation a gap is opened up by a viral at the cell memebrane to allow part of virus contaiing the viral genome to be transported into the cells 1st Mode 2nd Mode o Membrane fusion This mode only applies to viruses that carry their own membrane The viral membrane and cellular membrane fuse together in a way that allows the viral core coat protein nucleic acid from the exterior to the interior cell The subcellular location where membrane penetration occurs varies depending on the specific virus o Some viruses including bacteriophages and HIV cross the membrane at the cell surface while other viruses such as influenza virus penetrate the membrane inside the cells at vesicles called endosomes Both pore formation and membrane fusion can occur at either Process that delivers a virus from the plasma membrane to endosomes is location called endocytosis o Normal function of whice is the uptake of bulky materials from o Dropping the pH is usually required to trigger the fusion of the viral outside the cell membrane Transmembrane protein a protein that spans across the membrane lipid bilayer at least once Highly pathogenic avian influenza HPAI virus Avian flu virus that has crossed over from waterfowl to domestic birds and causes high rate of death in the latter population General steps of a virus life cycle o Entry this includes receptor binding all the way to the membrane o Replication of viral genomes which requires the expression of penetration replication enzymes o Viral assembly and exit which requires the expression of
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