Introduction to Viruses

• Peter Medawar, a Nobel laureate, described a virus as "a piece of bad news wrapped in protein."

Viruses

• In Latin, "virus" translates to "poison."

• Over 5,000 viruses have been identified, but it is estimated around 400,000 viruses exist.

• Viruses are ubiquitous, with 60,000 found in just one milliliter of ocean water.

• Viruses are not cells, and they do not independently exhibit the characteristics of living organisms.

• Viruses are small, obligate, intracellular parasites, requiring an electron microscope for visualization.

• One hundred million polio viruses could fit side by side on a period.

• Viruses must infect a host cell, hijacking its machinery to replicate.

• Viruses exhibit specificity, binding to a host cell through a receptor.

• Viruses can infect animals, plants, bacteria, fungi, protists and algae.

Viral Components

• Viruses contain nucleic acid, either DNA or RNA, which can be single or double stranded.
• They also possess a protein coat or capsid that protects the viral nucleic acid.
• Some animal viruses have a viral envelope derived from the host cell membrane.
• Spikes on the viral envelope aid in attachment to host cells.

Viral Morphologies

• Helical viruses consist of a spiral shape.
• Polyhedral, also known as icosahedral viruses, are spherical.
• Complex viruses are neither helical nor polyhedral.

Viral Replication

• Viruses multiply through replication.
• Bacteriophages are viruses infecting bacteria.
• Some viruses infect animal cells.

Bacteriophage Replication

• Viruses undergo lytic and lysogenic replication.
• Bacteriophages specifically infect bacteria.

Lytic Viral Replication

• T4 bacteriophage and E. coli (strain B) serve as the model for lytic replication.
• Lytic viral replication leads to the lysis, or bursting, of the host cell, releasing progeny viruses.

Steps in Lytic Viral Replication

1. Attachment happens when T4 and E. coli randomly collide, and T4 binds to a specific receptor on E. coli.
2. Entry occurs as T4 releases lysozyme to weaken E. coli's cell envelope, injecting its DNA.
3. Synthesis involves viral enzymes degrading E. coli DNA, utilizing the host's machinery to produce T4 components like capsids and DNA.
4. Assembly happens as T4 DNA is inserted into capsids.
5. Lysozyme finishes its action on the E. coli cell envelope during release, causing it to lyse, killing the cell, and releasing T4 progeny.

Lysogenic Viral Replication

• Lambda bacteriophage and E. coli (strain 12) serve as the model for lysogenic replication.
• Lysogenic viral replication begins and ends the same as lytic viral replication.

Steps in Lysogenic Viral Replication

1. Attachment is the same as in lytic replication.
2. Entry is the same as in lytic replication.
3. Insertion and Replication happens as lambda DNA integrates into the E. coli chromosome and is replicated along with it.
4. Induction happens as lambda DNA is excised from the E. coli chromosome due to exposure to UV light, x-rays, or gamma rays.

• E. coli* DNA is degraded.

5. Synthesis is the same as in lytic replication.
6. Assembly is the same as in lytic replication.
7. Release is the same as in lytic replication.

Steps in Animal Virus Replication

• Some, but not all, animal viruses have an envelope, which affects replication.

1. Attachment happens as spikes on an animal virus envelope enhance attachment, and the virus binds to a receptor on the host cell membrane.
2. Entry varies depending on the virus; three entry methods in an animal virus exist.

Mechanisms of Animal Virus Entry

• Direct penetration is used by some non-enveloped animal viruses where the virus binds to a receptor and injects nucleic acid into the host cell.
• Membrane fusion is used by enveloped animal viruses in which the viral envelope fuses with the host cell membrane, releasing the virus inside.
• Endocytosis is used by most enveloped and some non-enveloped animal viruses; the animal virus binds to a receptor, stimulating the host cell to engulf the virus.

3. Synthesis happens as the virus uses host cell machinery to produce viral capsids and nucleic acid.

• Retroviruses use reverse transcriptase to convert their RNA into DNA.
• The reverse transcriptase is a target for antiviral drugs.

4. Assembly happens as viral nucleic acid is inserted inside the capsid.
5. Release happens when non-enveloped animal viruses extrude from the cell via exocytosis, lysing the host cell.

• Enveloped viruses extrude via exocytosis, taking a portion of the host cell membrane with them to form their viral envelope.

Antiviral Medications

• Antiviral medications interfere with viral replication, by:
• Blocking attachment to the receptor on the host cell
• Blocking entry into host cell
• Blocking synthesis of viral components
• Preventing assembly
• Preventing release

Latency of Animal Viruses

• Animal viruses can enter a state of latency, as seen with Varicella-Zoster, Herpes, and Human Papilloma Virus.
• During latency, the virus is inactive and causes no symptoms, potentially lasting for decades.
• The virus can reactivate and cause symptoms from exposure to UV light or because of stress.
• Varicella-Zoster virus causes chicken pox and can reactivate to cause shingles.
• Some people get recurrent herpes and genital warts outbreaks.

Viruses and Cancer

• Viral infections cause 15-20% of human cancers.
• Human Papilloma Virus strains 16 and 18 were isolated from cervical cancer specimens in the 1980s.
• Epstein Barr Virus strains that cause mononucleosis contribute to Burkitt's lymphoma.
• Hepatitis B and C contribute to liver cancer.
• Cancer development requires "multiple hits," meaning, viral infections are just one factor among genetics, lifestyle, etc.

Prions

• Prions are infectious agents first noted when studying scrapie, a disease causing sheep to scrape their hindquarters raw.
• Stanley Prusiner identified it as protein with no nucleic acid, earning him the 1997 Nobel Prize and naming it a prion.
• Prions are solely made of protein.
• They induce abnormal folding of normal proteins in the brain, causing spongy brain with holes and brain damage, leading to loss of coordination, mental impairment, altered behavior, dementia, impaired senses, and delirium.
• Prion diseases are always fatal due to nerve cell damage and loss of brain function.
• Animal prion diseases:
• Scrapie in sheep
• Bovine spongiform encephalopathy or mad cow's disease
• Chronic wasting disease (deer, elk, moose)
• Transmissible mink encephalopathy
• Feline spongiform encephalopathy
• Prions are transmitted through body fluids via direct contact or environmental contamination of soil, food, or water.
• Human prion diseases include Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler-Scheinker disease, and Kuru.
• Creutzfeldt-Jakob can develop spontaneously, be inherited or contracted from consuming prion-infected animal meat.
• Gerstmann-Straussler-Scheinker disease comes from parents genetically.
• Kuru is spread by cannibalism of infected brain tissue.
• Diagnosis requires a brain or nervous tissue biopsy.
• There is no treatment or cure.
• Prions must be incinerated or autoclaved to be inactivated.