VIRO 1

• Viruses

  • Viruses are everywhere
  • Not all viruses cause disease
  • Estimated number of bacteriophages (viruses that infect bacteria) in the waters of the world is 1030
  • 8% of the human genome are viral in nature, called LTR retrotransponsons (only 3% of genes are expressed)
  • We are more virus than human
  • Some of these genes code for proteins that help us
• Viruses are microscopic intracellular parasites that lack the capacity to thrive and reproduce outside the host body
• Viruses are the smallest infectious agents (20-300 nm in diameter) that contain only one kind of nucleic acid (RNA or DNA) as their genome
• The entire infectious unit is called a virion

  • They are non-living outside the cell
• When they go inside the cell, they hijack the cell’s machinery to reproduce itself

  • They are not able to replicate themselves and they are dependent on the host cell
• Viruses do not have all the machinery needed for life

  • No ribosomes needed for protein synthesis
  • No enzymes needed for energy production
  • Lack many enzymes needed for reproduction
• Viruses only have genetic material that codes for its structural proteins and some essential enzymes they can use for reproduction
• Two Phases of viruses:

  1. Nonliving virus particle (virion)
  2. Living when inside the host cell
• How Were Viruses Discovered?

  • Before, scientists thought of viruses as toxins
  • In 1892, Ivanovsky created an experiment where he passed through the viral solution through a Chamberland filter
  • It only meant that bacteria are not the same as viruses,and there should be something much smaller than bacteria that cannot be cultured in broth but can still cause disease
  • Later on, they found out that when they transferred the substances to a calf, they would still manifest the symptoms.
• Chamberland filter


  excludes bacteria because it has low pore size, and they observed that it can still cause disease
• REMARKABLE VIRAL DISEASES

  • Polio
  • HIV
  • COVID-19
  • Cancers caused by viruses
• Types of viral symmetry

  • Cubic
  • Icosahedral - 20 faces, 12 vertices, vertex unit w/ 5-6 neighbors
  • spherical
  • Helical - protein subunits are bound in a periodic way, winding it into a helix
  • Complex
  • brick shape
  • complex shape
• RNA Viruses

  • dsRNA
  • Reoviridae
  • Picobimaviridae
  • (-) ssRNA
  • orthomyxoviridae
  • paramyxoviridae
  • rhaboviridae - bullet (rabies)
  • Bornaviridae - capsulated cubic shape
  • Filoviridae - filamentous
  • Bunyaviridae - segmented ssRNA
  • (+) ssRNA
  • hepeviridae
  • Caliciviridae
  • astroviridae
  • picornaviridae
  • coronaviridae
  • arteriviridae
  • togaviridae
  • flaviviridae
  • (RT) ssRNA
  • retroviridae
• DNA viruses

  • dsDNA
  • asfaviridae
  • poxviridae
  • iridoviridae
  • herpesviridae
  • polyomaviridae
  • papillomaviridae
  • adenoviridae
  • ssDNA
  • parvoviridae
  • circoviridae
  • (RT) dsDNA
  • hepadnaviridae
• Virus structure

  • genome - genetic material (DNA or RNA but not both)
  • capsid - protein shell or coat that encloses the NA genome
  • capsomere - morphologic units on the surface of icosahedral viruses
  • envelope - lipid-containing membrane acquired during viral maturation through a budding process
  • virion - complete virus particle

  
• Viral Protein


  • Structural proteins - facilitate transfer of viral nucleic acid, protection of viral genome against nucleases, attachment of virus, and structural symmetry (Ex. capsid)
  • Protein enzymes - present in very low amounts essential in initiation of viral replicative cycle
  • RNA polymerase - found in (-) RNA genomes and needed to copy the 1st mRNA
  • reverse transcriptase - enzyme in retroviruses and hepatitis viruses that makes a DNA copy of the viral RNA
  • Antigenic characteristics - hosts protective immune response is directed against proteins and glycoproteins expressed on the surface of virus particles
  • hemagglutinin - agglutinates RBCs (ex. influenza virus surface)
  • Transcription factors - bind to the host DNA consequently activation transcription or gene expression (ex. pox viruses)
• Viral nucleic acid

  • Viruses contain a single kind of nucleic acid (DNA or RNA)
  • Encodes the genetic information necessary for replication of the virus
  • Genome may be single- or double-stranded, segmented or non-segmented
  • Major characteristic in classifying viruses:
  • Type of nucleic acid (DNA or RNA)
  • Polarity (- or +)
  • Size (big or small)

  
• Viral lipid envelopes

  • Some viruses have envelopes
  • Acquired when viral nucleocapsid buds through a plasma membrane during maturation
  • The lipid-containing viruses are sensitive to treatment with ether and organic solvents
  • Loss of lipid results in loss of infectivity
  • This is because around the envelope there are attachment proteins. Once the envelope is destroyed, the virus can no longer attach to its host.
  • Nonlipid-containing viruses are generally resistant to ether and detergents
  • SARS-CoV-2 is enveloped
  • Hence, Handwashing and alcohol are effective ways to decrease viral load
• Viral Glycoproteins

  • Viral envelopes contain glycoproteins (“glyco” = sugar)
  • Example: spike protein of SARS-CoV-2 which is responsible for attaching to the ACE2 receptor in the lung cell
  • Virus-coded protein but host-derived sugars
  • Surface glycoproteins mediate attachment of the virus to the target cell through a cellular receptor
  • In HIV: binding of gp120 (viral glycoprotein) and CD4+ T Cell Receptor (and then binding of coreceptor)
  • Attachment leads to fusion of virus membrane and host membrane, thus allowing viral entry into the cell (lock and key model)

  
• GENERAL PRINCIPLES OF THE LIFE CYCLE OF VIRUSES

  • Life Cycle of Viruses: Attachment → Penetration → Biosynthesis → Maturation → Release
  • Attachment - proteins or glycoproteins in the virus particle attaches to a cell surface receptor
  • Penetrate - invade host cell
  • Biosynthesis - synthesize more genomes, more nucleic acid material, more proteins
  • Maturation - assemble and mature
  • Release
• Viral disease


  Some harmful abnormality that results from viral infection of the host organism
• Clinical disease


  Infection with overt (observable) signs and symptoms
• Syndrome


  Specific group of signs and symptoms; there should be a pattern to call it a syndrome
• Subclinical infection


  Symptoms in the host that fail to produce any symptoms; also called as asymptomatic infection
• Viral pathogenesis


  Process that occurs when a virus infects a cell and causes cellular disease; "patho" means disease and "genesis" emphasizes the beginning of that disease
• Disease pathogenesis


  Subset of events during an infection that results in disease manifestation in the host
• Pathogenic


  If the virus can infect and cause signs of disease in that host
• Virulent


  Commonly produces more severe disease in a susceptible host
• PRINCIPLES OF VIRAL DISEASES

  • Many viral infections are subclinical (asymptomatic)
  • The same disease syndrome may be produced by a variety of viruses (e.g. Flu and COVID-19 have similar symptoms such as fever and cough)
  • The same virus may produce a variety of diseases (e.g. chickenpox can be presented as the usual chickenpox but some can present as zoster virus etc.)
  • The outcome in any particular case is determined by both viral and host factors and is influenced by the environmental contexts and genetics of each
• TYPES OF HOST AND CELLULAR RESPONSES TO INFECTION

  Orange part - minimal visual changes on cellular level

  • Exposure but no attachment or cell entry - exposure without infection
  • viral multiplication without visible change or incomplete viral maturation - infection without clinical illness (asymptomatic)

  red part - discernible effect

  • significant effect on a cellular level (cellular transformation, dysfunction, inclusion body formation) - disease

  lysis of cells - death of organism

  
• STEPS IN VIRAL PATHOGENESIS

  • Entry and Primary Replication
  • Viral Spread and Cell Tropism
  • Cell Injury and Clinical Illness
  • Recovery from Infection
  • Virus Shedding
• STEP 1: ENTRY AND PRIMARY REPLICATION

  • Virus attach and enter cells in one of the body surfaces (usually the mucosa), or directly into tissues and bloodstream
  • e.g. Airborne transmission of viruses, needle infection of HIV
  • New virions are produced
  • New virions are released from the cell through lysis or shedding
  • The specific mechanisms are highly variable and more complex

  
• Viruses


  • Can produce disease at the portal of entry
  • Can spread systemically
• Mechanisms of viral spread


  1. Blood stream

  2. Lymphatics
• Viremia


  Presence of virus in the blood
• Viral Tropism


  Organ or cell-type specificities of virus
• Glycoproteins of the virus will have to bind to a certain receptor for it to successfully enter the cell
• If the cell does not have the receptor, it will not become infected
• Tissue and cellular tropism usually reflect the presence of specific cell surface receptors (components of the cell surface)
• STEP 3: CELL INJURY AND CLINICAL ILLNESS

  • Destruction of virus-infected cells in the target tissues
  • Examples:
  • COVID-19: destroy lung tissue → shortness of breath
  • HIV: destroy CD4 cells → susceptibility to opportunistic infections
  • CD4 cells are also called T cells which are the commanders of the immune system
  • Poliovirus: destroys motor neurons → paralysis
  • Fever is caused by the release of PNF and IL-1 cytokines in the bloodstream
  • General symptoms associated with viral illness: malaise and anorexia