Viruses Final 2.1 PDF

Going Viral  NOW LET’S GO VIRAL…. https://www.instagram.com/reel/C2Vs33BO4IU/?igsh=Y3R0dzE1YmhnOW9r https://www.instagram.com/reel/C2OJF1CqDjH/?igsh=MTM3YTJsMzVkeTAwNQ== DID YOU KNOW?  There are an estimated nonillion viruses in the world  Mammals & birds thought to host 1.7 million U...

Going Viral  NOW LET’S GO VIRAL…. https://www.instagram.com/reel/C2Vs33BO4IU/?igsh=Y3R0dzE1YmhnOW9r https://www.instagram.com/reel/C2OJF1CqDjH/?igsh=MTM3YTJsMzVkeTAwNQ== DID YOU KNOW?  There are an estimated nonillion viruses in the world  Mammals & birds thought to host 1.7 million UNDISCOVERED viruses  “Spillover event”- when viruses jump to humans  A little over 219 different viruses known to infect humans (2012)  Viruses in troposphere  WHY DO WE NEED VIRUSES?!  If we eliminated all viruses, we’d probably die in about 2 days  Most aren’t pathogenic to humans  Help with ecosystems, fungi, plants, etc.  Bacteriophages (viruses that infect bacteria) keep bacteria from taking over  By killing bacteria in the oceans, they allow plankton survive & produce oxygen  Oncolytic viruses  CLASS OBJECTIVES  Compare & contrast viruses & prokaryotic & eukaryotic organisms  List the definition, properties, consequences of viral properties  Be able to use basic terminology about viruses  Be able to describe how viruses are structured (capsid, envelope, etc.)  Be able to reference back to table & figures in this lecture as we begin to learn more specifics of each virus  Be able to apply the six stages of the establishment of infectious diseases to viruses  And elaborate on examples of encounter/entry, spread, damage, & three types of outcomes  Aka 4 main routes of entry, vertical vs. horizontal spread, physiological spread, & acute/chronic/latent infection outcome  Provide examples of the body’s intrinsic & extrinsic protective mechanisms  Describe the 6 steps of the viral life cycle and components of each  Describe basic differences between RNA & DNA viruses, positive sense & negative sense, & single stranded & double stranded  VIRUSES ARE NEITHER PRO NOR EUKARYOTIC BECAUSE THEY AREN’T “LIVING” THINGS CANNOT REPRODUCE BY THEMSELVES DEFINITIONS & PROPERTIES OF A VIRUS CONSEQUENCES OF VIRAL PROPERTIES  VIRAL STRUCTURE Knowledge of the structural (size and morphology) and genetic (type and structure of nucleic acid) features of a virus provides insight into how the virus replicates, spreads, and causes disease. Structures of a naked icosahedral capsid virus (top left) & enveloped viruses (bottom) with an icosahedral (left) nucleocapsid or a helical (right) ribonucleocapsid Helical nucleocapsids are always enveloped for human viruses  CAPSID MORPHOLOGY & THE ENVELOPE  Viral nucleic acid surrounded by a capsid (single- or double-layer protein shell)  Nucleic acid + capsid = nucleocapsid  Icosahedral- 20 triangular faces & 12 vertices subunits (soccer ball shape)  Helical- varied subunits, spherical core tight with specific viral capsid proteins  Viral envelope- membrane made of lipids, proteins, and glycoproteins  Nonenveloped (naked)- relatively stable & resistant to temp. changes, acids, proteases, detergents, & drying  Enveloped (not naked)- more fragile & susceptible to heat, acids, detergents & drying. MUST REMAIN WET & generally transmitted in fluids  Virus-specific envelope glycoproteins protrude from outer surface of envelope  i.e. SARS-CoV-2 spike protein  *You may see the term “head and tail” virus morphology, but they infect bacteria, not humans so we won’t learn that as a capsid shape VIRUS PARTICLE= VIRION  CLASSIFICATION Examples:  Structure  Picornavirus- pico “small” + rna “ribonucleic acid”  Togavirus- toga “mantle” (i.e. envelope)  Replication  Retrovirus- retro “reverse”  Location (of body)  Adenovirus- (adenoids)  Reovirus- Respiratory, Enteric, Orphan)  Location (place)  Norwalk virus- Norwalk, Ohio  Coxsackievirus- Coxsackie, New York Reovirus discovered before they knew it caused SPECIFIC disease, therefore they called it an Orphan virus  GLYCOPROTEINS  Most viral glycoproteins have asparagine-linked ( N -linked) carbohydrates and extend through the envelope and away from the surface of the virion  “Spike glycoproteins” (heard of this with Covid?)  Major antigens that elicit protective immunity  Some glycoproteins act as VAPs (Virus Associated Pyramids) that are capable of binging to structures on target cells  If they (VAPs) bind to erythrocytes = hemagglutinins (HAs)  Other glycoproteins include neuraminidase (NA; influenza), Fc receptor & C3b receptor (HSV)  Naked viruses can also express certain glycoproteins, even if they aren’t bound to envelop, just the capsid (i.e. adenoviruses) MAIN GROUPS OF HUMAN VIRUSES REFER TO TABLE PRINT IT OUT.. POST IT EVERYWHERE, VERY HELPFUL. TEST YOUR KNOWLEDGE #1  What are the two capsid shapes?  Icosahedral & helical Encounter Entry WHO REMEMBERS THE Spread SIX STAGES OF Multiplication ESTABLISHMENT OF INFECTIOUS Damage DISEASE?! Outcome  ENCOUNTER & ENTRY  4 Main Routes:  Respiratory  Gastrointestinal  Transcutaneous  Sexual  Exogenous vs. Endogenous Virus  Most viral diseases come from Exo  Endo= reactivation of latent virus from within host cell i.e. HSV, VZV (shingles)  SPREAD & MULTIPLICATION (AKA REPLICATION)  Vertical vs. Horizontal spread (more like how the virus spreads amongst people)  Vertical- fetus infected in-utero  Horizontal- between members of susceptible host population  Physiological spread  Neural- virus spreads through nerves, i.e. HSV, rabies,VZV  Hematogenous- carried in the blood, i.e. CMV, HIV, EBV  High titer in bloodstream=viremia  *Exception, some viruses have multiple pathways for spread, i.e.VSV skin & neural  Incubation Period- the period between exposure to an infection and the appearance of the first symptoms  DAMAGE  Signs & symptoms of viral disease are culmination of a series of interactions between virus & host  Intrinsic protective mechanisms:  Apoptosis  Autophagy (“self ” “eating”)- cellular stress response viral sequestration & degradation in cytoplasmic organelles called autophagosomes  Extrinsic protective mechanisms:  Barriers  Innate immune responses-  Toll like receptors (TLRs)- pattern recognition receptors that identify conserved patterns in pathogens  Interferon- inhibit virus replication indirectly by inducing the expression of cellular proteins that inhibit the protein synthesis machinery  Cell-mediated immunity- NK cells (innate), Cytotoxic T-cells (adaptive)  Adaptive immune response  Neutralizing antibodies (destroy infectivity of virus)  Antibody-dependent cell-mediated cytotoxicity- antibodies lyse virus infected cells OUTCOME  Three types of viral infections:  Acute infection- virus undergoes multiple rounds of replication, results in death of host cell OR host successfully controls virus  Chronic infection- virus particles continue to shed after acute illness, sometimes without host death; host doesn’t successfully control virus  Usually RNA viruses  Latent infection- does not result in production of progeny viruses; host may or may not have “controlled” virus  DNA viruses or retroviruses  Can reactivate  Can cause cellular transformation -> cancer TEST YOUR KNOWLEDGE #2 VIRAL LIFE CYCLE 1. Attachment 2. Entry 3. Uncoating 4. Synthesis of protein & nucleic acid 5. Assembly 6. Release  1. ATTACHMENT & 2. ENTRY & 3. UNCOATING  Attachment: Virus attaches to host cell adhesion receptors on surface  Enveloped viruses: use surface spike proteins  One or more attachment proteins  Naked viruses: surface-exposed capsid regions mediate attachment  Tissue tropism- Bind to specific receptor(s)  Entry: Virion moves along host cell surface where it encounters entry receptors (aka co-receptors)  Membrane fusion: Fuses with host membrane & nucleocapsid is released  OR Endocytosis & virus is uncoated inside cell  Uncoating: virions disassembled. Capsid is removed to make viral genome accessible to the cellular transcription & translation machinery * There are exceptions, but wait until we learn those individual viruses  4. SYNTHESIS OF PROTEIN & NUCLEIC ACID  Depends on if virus is single- or double-stranded & DNA or RNA (we’ll learn more later)  This will be useful for later when we learn the different viruses (so keep it in mind for later/reference)  VIRAL NUCLEIC ACID & “SENSES”  Comprise the viral genome  DNA viruses  DNA viruses move to the nucleus for genome replication (poxviruses are an exception)  Immediate-early and early transcription produces the enzymes and proteins needed for late transcription  Early transcription is followed by genome replication.  Late transcription produces the capsid structural proteins.  Show that assembly results in the formation of the nucleocapsid.  RNA viruses  Most RNA viruses replicate in the cytoplasm (exceptions include influenza and retroviruses). Most are single-stranded.  The RNA virus genome encodes RNA-dependent RNA polymerases as well as the enzymes necessary for viral mRNA processing.  Self-assembly of the genome and structural proteins produces the nucleocapsid.  Classified according to the polarity of their RNA  Positive-sense strand viral genomes act as mRNA for protein synthesis, so translation can begin immediately.  Naked positive-sense viral genomes are infectious.  Negative-sense strand viral genomes do not immediately begin transcription. Like templates for messenger RNA that have to be transcribed into positive RNA Act as a template for synthesis of a positive-sense strand, which is then used for protein synthesis.  Naked negative-sense strand viral genomes are not infectious by themselves. ***Be aware that there are exceptions and complications to this classification system  VIRAL GENETICS  Recombination- Genetic information is exchanged between viruses or a virus and its host.  Reassortment- Viruses with segmented genomes create a hybrid strain.  This can lead to antigenic shift; E.g. H5N1 Bird flu  Complementation- Gene products or functions of a mutated virus are complemented by another virus.  A mutated virus is non-functional until its complement virus arrives and produces a protein or function that is beneficial to both.  E.g. Hepatitis D relies on replicating Hepatitis B to provide its envelope protein.  Phenotypic mixing- A virus genome is partially or completely coated with surface proteins of a different virus.  Be aware that the progeny of this virion will have a protein coat that matches its genome.  6. RELEASE (& M PROTEIN & VIRAL BUDDING)  Release  Nonenveloped- usually when then cell lyses  Lytic virus – burst out of host cell killing it  In contrast to “Lysogenic virus”  Lysogenic virus – integrate into host genome and are replicated when it is replicated; like “hitching a ride” or a “Trojan horse” until conditions trigger it to produce new virus particles  Exocytosis- reverse phagocytosis  Enveloped- budding out of host cell; Some cause apoptosis, some are non-lethal  M-protein- inner surface of envelope & touches nucleocapsid  Stabilize glycoprotein & lipid envelope interaction  Direct viral genome to sites of virus assembly  Help virus budding TEST YOUR KNOWLEDGE #2  What are the 6 steps of viral replication?  Attachment  Entry  Uncoating  Synthesis of protein & nucleic acid  Assembly  Release ALSO A SCIENTIST Rebecca Lee Crumpler, MD (1831-1895) MD from New England Female Medical College  1864- First African-American woman to earn an MD  1883- Published “Book of Medical Discourses,” one of the very first medical publications by an African American  “It may be well to state here that, having been reared by a kind aunt in Pennsylvania, whose usefulness with the sick was continually sought, I early conceived a liking for, and sought every opportunity to relieve the sufferings of others.”