Viruses, Viroids, and Prions

Are Viruses Living or Non-living? They have some properties of life but not others For example, viruses can be killed, even crystallized like table salt However, they can’t maintain a constant internal state (homeostasis).

What are Viruses? A virus is a non-cellular particle made up of genetic material and protein that can invade living cells.

Viral History

Discovery of Viruses Beijerinck (1897) coined the Latin name “virus” meaning poison He studied filtered plant juices & found they caused healthy plants to become sick

Tobacco Mosaic Virus Wendell Stanley (1935) crystallized sap from sick tobacco plants He discovered viruses were made of nucleic acid and protein

Smallpox Edward Jenner (1796) developed a smallpox vaccine using milder cowpox viruses Deadly viruses are said to be virulent Smallpox has been eradicated in the world today

Viewing Viruses Viruses are smaller than the smallest cell Measured in nanometers Viruses couldn’t be seen until the electron microscope was invented in the 20th century

Size of Viruses

Viral Structure

Characteristics Non living structures Noncellular Contain a protein coat called the capsid Have a nucleic acid core containing DNA or RNA Capable of reproducing only when inside a HOST cell

Characteristics Some viruses are enclosed in an protective envelope CAPSID Some viruses are enclosed in an protective envelope Some viruses may have spikes to help attach to the host cell Most viruses infect only SPECIFIC host cells DNA ENVELOPE SPIKES

Characteristics Viral capsids (coats) are made of individual protein subunits Individual subunits are called capsomeres CAPSOMERES

Characteristics Outside of host cells, viruses are inactive Lack ribosomes and enzymes needed for metabolism Use the raw materials and enzymes of the host cell to be able to reproduce EBOLA VIRUS HIV VIRUS

Characteristics Some viruses cause disease Smallpox, measles, mononucleosis, influenza, colds, warts, AIDS, Ebola Some viruses may cause some cancers like leukemia Virus-free cells are rare MEASLES

Viral Shapes Viruses come in a variety of shapes Some may be helical shape like the Ebola virus Some may be polyhedral shapes like the influenza virus Others have more complex shapes like bacteriophages

Helical Viruses

Polyhedral Viruses

Complex Viruses

Taxonomy of Viruses

Viral Taxonomy Family names end in -viridae Genus names end in -virus Viral species: A group of viruses sharing the same genetic information and ecological niche (host). Common names are used for species Subspecies are designated by a number

Viral Taxonomy Examples Herpesviridae Herpesvirus Human herpes virus 1, HHV 2, HHV 3 Retroviridae Lentivirus Human Immunodeficiency Virus 1, HIV 2

Herpes Virus SIMPLEX I and II

Adenovirus COMMON COLD

Influenza Virus

Chickenpox Virus

Papillomavirus – Warts!

Used for Virus Identification RNA or DNA Virus Do or do NOT have an envelope Capsid shape HOST they infect

Bacteriophages

Phages Viruses that attack bacteria are called bacteriophage or just phage T-phages are a specific class of bacteriophages with icosahedral heads, double-stranded DNA, and tails

T-phages The most commonly studied T-phages are T4 and T7 They infect E. coli , an intestinal bacteria Six small spikes at the base of a contractile tail are used to attach to the host cell Inject viral DNA into cell

Escherichia Coli Bacterium T - EVEN PHAGES ATTACK THIS BACTERIUM

T-Even Bacteriophages

Diagram of T-4 Bacteriophage Head with 20 triangular surfaces Capsid contains DNA Head & tail fibers made of protein

Retroviruses

Characteristics of Retroviruses Contain RNA, not DNA Family Retroviridae Contain enzyme called Reverse Transcriptase When a retrovirus infects a cell, it injects its RNA and reverse transcriptase enzyme into the cytoplasm of that cell

ENZYME

Retroviruses The enzyme reverse transcriptase (or RTase), which causes synthesis of a complementary DNA molecule (cDNA) using virus RNA as a template RTase

Retroviruses HIV, the AIDS virus, is a retrovirus Feline Leukemia Virus is also a retrovirus

Viroids & Prions

Viroids Small, circular RNA molecules without a protein coat Infect plants Potato famine in Ireland Resemble introns cut out of eukaryotic

Prions Prions are “infectious proteins” They are normal body proteins that get converted into an alternate configuration by contact with other prion proteins They have no DNA or RNA The main protein involved in human and mammalian prion diseases is called “PrP”

Prion Diseases Prions form insoluble deposits in the brain Causes neurons to rapidly degeneration. Mad cow disease (bovine spongiform encephalitis: BSE) is an example People in New Guinea used to suffer from kuru, which they got from eating the brains of their enemies

Viral Replication

Viral Attack Viruses are very specific as to which species they attack HOST specific Humans rarely share viral diseases with other animals Eukaryotic viruses usually have protective envelopes made from the host cell membrane

5 Steps of Lytic Cycle 1. Attachment to the cell 2. Penetration (injection) of viral DNA or RNA 3. Replication (Biosynthesis) of new viral proteins and nucleic acids 4. Assembly (Maturation) of the new viruses 5. Release of the new viruses into the environment (cell lyses)

Bacteriophage Replication Bacteriophage inject their nucleic acid They lyse (break open) the bacterial cell when replication is finished

Lytic Cycle Review Attachment Phage attaches by tail fibers to host cell Penetration Phage lysozyme opens cell wall, tail sheath contracts to force tail core and DNA into cell Biosynthesis Production of phage DNA and proteins Maturation Assembly of phage particles Release Phage lysozyme breaks cell wall

1 2 3 Bacterial cell wall Bacterial chromosome Capsid DNA Capsid Sheath Tail fiber 1 Attachment: Phage attaches to host cell. Tail Base plate Pin Cell wall Plasma membrane 2 Penetration: Phage pnetrates host cell and injects its DNA. Sheath contracted Tail core 3 Merozoites released into bloodsteam from liver may infect new red blood cells

4 5 Tail DNA Maturation: Viral components are assembled into virions. Capsid 5 Release: Host cell lyses and new virions are released. Tail fibers

One-step Growth Curve If all 500 viruses released attach to new cells, how many viruses could there be in the body at the end of the next 40 minute cycle?

Viral Latency Some viruses have the ability to become dormant inside the cell Called latent viruses They may remain inactive for long periods of time (years) Later, they activate to produce new viruses in response to some external signal (stress, illness, etc.) HIV, Herpes, and chickenpox (causes shingles) viruses are examples

Lysogenic Cycle Phage DNA injected into host cell Viral DNA joins host DNA forming a prophage When an activation signal occurs, the phage DNA starts replicating

Lysogenic Cycle Viral DNA (part of prophage) may stay inactive in host cell for long periods of time Replicated during each binary fission Over time, many cells form containing the prophages

Viral Latency Once a prophage cell is activated, host cell enters the lytic cell New viruses form & the cell lyses (bursts) Virus said to be virulent (deadly) ACTIVE STAGE INACTIVE STAGE

Virulent Viruses HOST CELL LYSES & DIES

The Lysogenic Cycle

Latency in Eukaryotes Some eukaryotic viruses remain dormant for many years in the nervous system tissues Chickenpox (caused by the virus Varicella zoster) is a childhood infection It can reappear later in life as shingles, a painful itching rash limited to small areas of the body SHINGLES

Latency in Eukaryotes Herpes viruses also become latent in the nervous system A herpes infection lasts for a person’s lifetime Genital herpes (Herpes Simplex 2) Cold sores or fever blisters (Herpes Simplex 1) SKIN TO SKIN CONTACT PASSED AT BIRTH TO BABY

VIRUS DESTROYING HOST CELL Virulence VIRUS DESTROYING HOST CELL

Lytic and Lysogenic Cycles

Body’s Defense Against Disease Causing Agents

First Line of Defense Skin, mucous, cilia, stomach acid, and saliva Think of the human body as a hollow plastic tube… The food is digested within the hole in the tube, but it never actually enters into the solid plastic material. Tube inner surface ~Digestive System~ Tube inner surface ~Digestive System~ Tube inner surface ~Digestive System~

Second Line of Defense ~White Blood Cells~ If invaders actually get within the body, then your white blood cells (WBCs) begin their attack WBCs normally circulate throughout the blood, but will enter the body’s tissues if invaders are detected

White Blood Cells ~Phagocytes~ These white blood cells are responsible for eating foreign particles by engulfing them Once engulfed, the phagocyte breaks the foreign particles apart in organelles called Lysosomes

The Second Line of Defense ~Interferon~ Virus-infected body cells release interferon when an invasion occurs Interferon – chemical that interferes with the ability to viruses to attack other body cells

White Blood Cells ~T-Cells~ T-Cells, often called “natural killer” cells, recognize infected human cells and cancer cells T-cells will attack these infected cells, quickly kill them, and then continue to search for more cells to kill

The Second Line of Defense ~The Inflammatory Response~ Injured body cells release chemicals called histamines, which begin inflammatory response Capillaries dilate Pyrogens released, reach hypothalamus, and temperature rises Pain receptors activate WBCs flock to infected area like sharks to blood

Two Divisions of the Immune System The efforts of the WBCs known as phagocytes and T-cells is called the cell-mediated immune system. Protective factor = living cells Phagocytes – eat invaders T-cells – kill invaders

Two Divisions of the Immune System The other half of the immune system is called antibody-mediated immunity, meaning it is controlled by antibodies This represents the third line of defense in the immune system

The Third Line of Defense ~Antibodies~ Most infections never make it past the first and second levels of defense Those that do trigger the production and release of antibodies Proteins that latch onto, damage, clump, and slow foreign particles Each antibody binds only to one specific binding site, known as an antigen

Antibody Production WBCs gobble up invading particles and break them up They show the particle pieces to T-cells, who identify the pieces and find specific B-cells to help B-cells produce antibodies that are equipped to find that specific piece on a new particle and attach

What is immunity? Resistance to a disease causing organism or harmful substance Two types Active Immunity Passive Immunity

Immunity New particles take longer to identify, and a person remains ill until a new antibody can be crafted Old particles are quickly recognized, and a person may never become ill from that invader again. This person is now immune.

Active Immunity You produce the antibodies Your body has been exposed to the antigen in the past either through: Exposure to the actual disease causing antigen – You fought it, you won, you remember it Planned exposure to a form of the antigen that has been killed or weakened – You detected it, eliminated it, and remember it

Vaccines An attenuated virus is a weakened, less vigorous virus “Attenuate" refers to procedures that weaken an agent of disease (heating) A vaccine against a viral disease can be made from an attenuated, less virulent strain of the virus Attenuated virus is capable of stimulating an immune response and creating immunity, but not causing illness

Vaccine Antigens are deliberately introduced into the immune system to produce immunity Because the bacteria has been killed or weakened, minimal symptoms occur Have eradicated or severely limited several diseases from the face of the Earth, such as polio and smallpox

How long does active immunity last? It depends on the antigen Some disease-causing agents multiply into new forms that our body doesn’t recognize, requiring annual vaccinations, like the flu shot Booster shot - reminds the immune system of the antigen Others last for a lifetime, such as chicken pox

Think the flu is no big deal? Think again… In 1918, a particularly deadly strain of flu, called the Spanish Influenza, spread across the globe It infected 20% of the human population and killed 5%, which came out to be about 100 million people

Do we get all the possible vaccines we can? Although the Center for Disease Control (CDC) recommends certain vaccines, many individuals go without them Those especially susceptible include travelers and students Consider the vaccine for meningitis, which is recommended for all college students and infects 3,000 people in the U.S., killing 300 annually

Passive Immunity You don’t produce the antibodies A mother will pass immunities on to her baby during pregnancy - through what organ? These antibodies will protect the baby for a short period of time following birth while its immune system develops. What endocrine gland is responsible for this? Lasts until antibodies die Thymus Placenta Why doesn’t the mother just pass on the WBCs that “remember” the antigens?

Acquired Immune Deficiency Syndrome Caused by the Human Immunodeficiency Virus Discovered in 1983 Specifically targets and kills T-cells Because normal body cells are unaffected, immune response is not launched

AIDS ~The Modern Plague~ The HIV virus doesn’t kill you – it cripples your immune system With your immune system shut down, common diseases that your immune system normally could defeat become life-threatening Can show no effects for several months all the way up to 10 years

AIDS ~The Silent Spread~ Transmitted by sexual contact, blood transfusions, contaminated needles As of 2007, it affects an estimated 33.2 million people

Other Viral Treatments Interferon are naturally occurring proteins made by cells to fight viruses Genetic altering of viruses (attenuated viruses) Antiviral drugs (AZT) Protease inhibitors – prevent capsid formation