• Initially meant "poison" or "poisonous slime"
• Now referred to as sub-microscopic agents that cannot multiply unless it invades a specific host cell and utilizes its machinery.
• Typically causes harm to the cell that is infected.
• Classified by the types of cells they infect: eukaryotic or prokaryotic cells
• Viruses that infect bacteria are bacteriophages
• Eukaryotic viruses infect many types of eukaryotic cells (ex. Algal cells)
• The most numerous biological entity on earth and are ecosystem architects

• Sub-microscopic: smaller than even the smallest bacteria and can't be seen by light microscopes
• 10-1000x smaller than the cells they infect

• We focus on disease-causing animal viruses, but there are many others with many other role
• Bacteriophages regulate salt and freshwater ecosystems by destroying aquatic bacteria; this leads to the recycling of carbon

• Can be found inside and outside of host cells (inert outside the cell) -> in order to function, virus must infect a host cell within the cell and use its machinery to reproduce --> makes it "nonliving"
• "Nonliving" aspect gives specific terminology:
• Viruses are called "infectious particles," "active/inactive" instead of living.
• Active/inactive nature of viruses makes study complicated as they must be cultivated in host cells for study.

What are acute infections?

1. acute infections cause visible symptoms suddenly for a relatively short duration
1. a burst of variants being released from an infected host cell causes symptoms (a combination of localized/widespread tissue damage following cell death and damaged tissue due to immune response)
2. Ex: influenza, mumps virus

1. Infections that can continue with or without symptoms for years or an entire life span; does not cause lysis
1. Cytopathic effects: eukaryotic viruses that cause damage to host cells and tissues that don’t cause lysis
1. Ex: multiple nuclei in one cell by fusion of multiple host cells
2. Chronic: continuous release of low levels of viral particles where there’s an absence of disease symptoms (contagious)
1. Ex: hepatitis B
3. Latent
   

1. viral genome remains silent within host cells but can reactivate to cause damage can’t be eradicated from the body (ex. cold sores)
1. Can be done by integration into the genome of the host cell (pro virus)
2. Can also be done by replicating independently of the host genome (ex. plasmid)

chicken pox and shingles are caused by varicella zoster virus, and shingles is a reactivated form of chicken pox

1. Viral infections can trigger the transformation (oncogenesis) of a host cell into a malignant cell that has the potential to cause cancer (unregulated cell growth)
1. Oncogenes: viruses that carry genes for cell growth
2. Bear in mind that most tumors are caused by mutations in the host genome
3. Ex: HPV

No, some are used to treat bacterial infections (ex: phages)

1. History of viruses
1. Early studies of viruses started with the Tobacco mosaic virus (virus that damages plants) and there were thoughts that it was a bacterium due to its contagious nature.
2. When put through a filter holding bacteria, it was found that viruses are smaller than bacteria and that it was the culprit. Same process was used to identify foot and mouth disease.

1. All viruses have a protein capsid in common, which surrounds the nucleic acid

1. Envelope: lipid layer that is often a modified piece of the host cell membrane

1. Capsomers: what capsids are composed of; they are identical protein subunits.

• Nucleocapsid: nucleic acid (DNA or RNA) + capsid (protects and helps with transfer between host cells)

• Viral genome range vary greatly in size (nucleic acid)
• Cellular genomes: double stranded DNA
• Viral genomes have 4 possible nucleic acid types
• Double (herpes) and single (HPV) stranded DNA -> double is most common, both can be linear or circular (can switch from one form to the other)
• Single (SARS) and double stranded RNA -> single more common
• Segmented genomes: genomes that consist of more than one segment of RNA (influenza); each segment codes for one protein and all sit in the same capsid

1. Envelope: lipid layer that is often a modified piece of the host cell membrane
1. Arise from the plasma or nuclear membrane of the host cell, so envelope carbs and lipids are taken from the host, and envelope proteins are coded for by viral genes and may protrude from the envelope -> spikes
1. Spikes: involved in attaching the virus to the host cell surface
1. Influenza spikes: enzyme neuraminidase (11 subtypes N1 - N11) which releases variants into host cells and hemagglutinin proteins (at least 18 subtypes H1 - H18) that bind to host cells

1. Capsid symmetry: how the capsomers are arranged
1. Helical: hollow tubes with protein walls (ex: tobacco mosaic virus; also happens to be a naked virus). Encloses an RNA genome wound in a spiral.
1. Influenza is enveloped and is not as rigid as tobacco mosaic due to the multiple capsids in one envelope. This makes influenza flexible.

1. Icosahedral: regular polyhedron in triangular shapes (ex: adenovirus (naked), herpes (enveloped))

1. Complex: most viruses have a helical or icosahedral, so complex viruses are those that do not belong in either category (ex: poxviruses (smallpox), phages)
   
   1. Poxvirus: lack a capsid and are covered by lipoproteins and fibrils on the surface
   2. Bacteriophages: have a polyhedral capsid head and a helical tail with fibrous attachments to the host cell (looks like a spider)

Understand how viruses are classified and grouped (brought upon by the electron microscope) -> see images

1. Nucleic acid type
2. Presence/absence of envelope: spikes vary in appearance per virus and thus can be used for classification.
1. Dimensions of virion (complete infectious virus particle) and capsid symmetry/arrangement
   1. Virions are diverse in shape and size primarily due to capsid symmetry and the presence of an envelope.

• Louis Pasteur developed its vaccine without knowing what a virus was (a non-living thing)
• Outcome is almost always death
• Infects all warm-blooded animals
• Human rabies has two forms:
• Furious rabies symptoms—bizarre behavior like biting, anxiety, hallucinations, agitation, difficulty swallowing, fear of water
• Paralytic

Describe the 5-step infection cycle for enveloped and non-enveloped viruses.

1. Attachment of virus to host cell

2. Variant Penetration and uncoating within the host cell

3. Synthesis of viral proteins and replication of viral nucleic acid

4. Assembly and maturation of variants

5. Variant release from the host cell

1. Attachment of virus to host cell: spike protein binds to receptors on the host cell surface
1. Cellular and tissue tropism: when receptors specificity restricts host cell and tissue types that a virus can attach to.
2. Viral host range/host tropism: most viruses can only infect a single species

Infection cycle: 

Variant Penetration and uncoating within the host cell

1. entry of virion into cell depends on whether virus is enveloped or naked
1. Enveloped: can enter by membrane fusion or endocytosis
1. Membrane fusion
1. spikes of virion attach to specific host cell receptors
2. Envelope of virion fuses with cytoplasmic membrane of host cell
3. Nucleocapsid is released into cytoplasm and the viral envelope stays with the membrane
4. Nucleic acid separates from capsid (uncoating)
2. Endocytosis (naked cells also enter via this method due to no envelope using capsid proteins)
1. Attachment receptors of host cell trigger endocytosis
2. Membrane surrounds the virion and forms an endocytic vesicle
3. Envelope of virion fuses with endosomal membrane
4. Nucleic acid separates from capsid (uncoating)

1. the bringing together of the newly formed viral nucleic acid with capsid proteins, and packaging them into a capsid to form a nucleocapsid for new virions
1. Assembly process of virions
1. Spontaneous self-assembly when a specific amount of viral nucleic acid and capsid protein have accumulated in the host cell
2. Self-assembly of the new variant occurs in a step-wise manner
2. Site of assembly and maturation depend on the virus and how variants are released from the host cells (ex: some finish the process after release)

Infection cycle: Variant release from the host cell

1. also dependent on virus enveloped or naked
1. Budding: performed by enveloped viruses and the cell survives to potentially make more variants
1. Viral encoded proteins incorporate into the host cell membrane
2. The nucleocapsid is released the same time the envelope is formed by budding of membrane
2. Lysis: occurs with some naked animal viruses with bacteriophages
1. Cell death occurs in different ways. Examples:
1. virus can trigger apoptosis -> program the cell to kill itself to protect the body, but that only releases the variants (bacteriophages)

Infection cycle: Synthesis of Viral Proteins and Replication

• Producing viral particles requires 2 events
• Viral gene expression to produce viral proteins (e.g Capsid proteins, replication enzymes)
• Synthesis of copies of viral genome

Viral replication strategy (the way they replicate)

dependent on the type of virus: DNA virus, RNA virus, or reverse-transcribing virus

1. DNA virus (single or commonly double-stranded)
1. Usually replicates in the nucleus
2. Requires host machinery for DNA synthesis and gene expression but encodes its own polymerase
• +- ds DNA: the double stranded (ds) DNA of a virus; made of a negative strand that serves as the template for transcription and a positive strand for genome synthesis.
• Transcription is when an enzyme uses one strand of DNA as a template to make a positive strand of single stranded (ss) mRNA, which is then translated to make proteins.
• Replication of a ssDNA virus requires the synthesis of a complementary strand to form a ds DNA molecule. Then transcription and protein synthesis occurs.
• Newly generated ss can also serve as a template for future viral genomes (ex. Replication)

1. RNA virus (single stranded)
• Usually replicates in the cytoplasm.
• Requires replicase -> virally-encoded RNA-dependent RNA polymerase; uses an RNA template to synthesize a new strand of RNA from parent RNA strand.
• Replication strategy depends on type of RNA virus
• Types of RNA viruses
2. +ssRNA,  -ssRNA, and 
   +/-dsRNA viruses

1. +ssRNA viruses replication strategy is similar to mRNA due to similar genome
1. Viral RNA binds to host cell ribosomes where it's translated to make copies of its proteins
2. One of the proteins transcribed is a viral replicase that can synthesize more copies of the viral genome by making a complementary -ssRNA from original positive strand template.
3. -ssRNA is then used as a template to make more +ssRNA
1. can make more proteins (such as viral replicase to make more +ssRNA or is packaged within the genome (which is in the capsid) for new variants

can't be translated directly; must be copied into +ssRNA strand by carrying its own replicase into the host cell. Replicase produces +ssRNA strand and can make more proteins or is packaged within the genome for new variants WITH the replicase (otherwise -ssRNA variants will not be able to replicate).

1. (uncommon): also carry their own replicase into the host cell because the host cell is unable to translate dsRNA.
1. Replicase uses the -RNA strand as a template to make +ssRNA
2. Either translated to make more replicase or +/-dsRNA

1. Retroviruses: reverse transcribing viruses (e.g HIV)
1. Encode a reverse transcriptase -> RNA dependent DNA polymerase that synthesizes DNA from an RNA template (in regular transcription, RNA is synthesized from DNA template).
2. Have +ssRNA strand genome (viruses) and carry reverse transcriptase in the variant.
1. Upon entry in the host cell, the reverse transcriptase uses the RNA genome (+ssRNA) as a template to make one strand of DNA (-ssDNA).
2. Compliment to that DNA strand is synthesized to ssRNA and integrates into the host cell chromosome.
3. Can be latent (dormant) or transcribed into RNA that is translated to make viral proteins for new variants; DNA is permanent (cannot be eliminated from the cell).

• DNA polymerase is DNA dependent; has proofreading ability
• Replicases are RNA dependent; lack proofreading ability and therefore make more mistakes during replication
  • Mutations lead to antigenic variation and allow some RNA viruses to adapt under new selective pressures -> ex. Influenza cause a type of antigenic variation called antigenic drift
  • Antigenic drift
  • Antigenic shift

Antigenic drift and antigenic shift

• Antigenic drift: occurs when mutations accumulate in the genes encoding key viral surface proteins such as spike proteins.
• Surface proteins enable the host immune system to recognize the virus -> the reason why we have a new flu vaccine every year.
• Antigenic shift: other type of antigenic variation
  • RNA viruses undergo more profound changes through the reassortment of their genomes
  • Segmented genomes with more than one piece of RNA; occurs when two different strains of the same virus infect the same host cell mixing pieces of their genomes together during replication (reassortment).
  • Ex: swine flu (swine + human reassortment)