Viruses

Historical Context and Discovery of Viruses

• Etymology of "Virus": In Latin, the term "virus" translates directly to "poison" or "venom."

• Discovery Milestones:

  • The first viral discovery is attributed to Dmitri Ivanovski, a Russian botanist, in 1892.

  • Ivanovski studied the sap of tobacco plants affected by tobacco mosaic disease (TMD).

  • He discovered that the disease could be transmitted to healthy plants via a "filterable component" that was significantly smaller than any known bacterium.

General Characteristics of Viruses

• Status as Pathogens: Viruses are classified as nonliving, acellular (they do not consist of cells), submicroscopic, infectious agents.

• Obligate Intracellular Pathogens: They always require a living host cell to multiply; they cannot reproduce independently.

• Virology: This is the formal field of study dedicated to viruses.

• Diversity and Impact:

  • Over 5,000 mammal-infecting viral species have been described to date.

  • Approximately 220 of these species are known to infect humans.

  • It is estimated that at least 320,000 mammalian viruses remain uncharacterized.

  • Roughly 70 % of viruses that infect humans are harbored in other animal populations.

• Structural and Metabolic Limitations:

  • Viruses are extremely small, typically ranging from $20$ to $400\,nm$.

  • They contain either DNA or RNA, but not both.

  • They possess a protein coat (capsid).

  • They lack ribosomes.

  • They lack any mechanisms for generating ATP.

Viral Sizes and Comparative Scale

• Size Ranges:

  • Rhinoviruses and polioviruses: Diameter as small as $30\,nm$.

  • Human Immunodeficiency Virus (HIV): Approximately $120\,nm$.

  • Bacteriophage T4: Approximately $225\,nm$.

  • Ebola virus: Approximately $970\,nm$ in length.

  • Pandoraviruses: Lengths nearing $1,000\,nm$.

  • Pithovirus (discovered in 2014): One of the largest known viruses, measuring $1,500\,nm$ in length.

• Biological Comparisons for Scale:

  • Human red blood cell: Typical diameter of $8,000\,nm$.

  • E. coli bacterium: Typical length of $2,000\,nm$.

Comparison of Viruses, Prokaryotes, and Eukaryotes

• Cells: Viruses (No); Prokaryotes (Yes); Eukaryotes (Yes).

• Considered Alive: Viruses (No); Prokaryotes (Yes); Eukaryotes (Yes).

• Relative Size:

  • Viruses: Generally smaller than prokaryotes; most require electron microscopy to be seen.

  • Prokaryotes: Most are bigger than viruses and smaller than eukaryotes; usually visible via light microscopy.

  • Eukaryotes: Usually bigger than prokaryotes and viruses; often visible via light microscopy.

• Filterability: Viruses pass through a filter; Prokaryotes generally do not (with exceptions like Mycoplasma species); Eukaryotes do not.

• Structure:

  • Viruses: Protein capsid coating and nucleic acid.

  • Prokaryotes: Cells without nuclei or other membrane-bound organelles.

  • Eukaryotes: Cells with nuclei and membrane-bound organelles.

• Replication:

  • Viruses: Host cell energy and machinery are hijacked to replicate the virus.

  • Prokaryotes: Binary fission (asexual).

  • Eukaryotes: Mitosis (asexual) and Meiosis (sexual).

• Metabolism: Viruses (No); Prokaryotes (Yes); Eukaryotes (Yes).

• Genome Composition: Viruses (DNA or RNA); Prokaryotes (DNA); Eukaryotes (DNA).

Viral Structure and Virion Components

• Virion: A complete, individual virus particle.

• Core Components:

  • Nucleic Acid Core: The genetic material (DNA or RNA).

  • Capsid: An outer protein coating.

  • Envelope (Optional): An outer layer made of phospholipid membranes derived from the host cell, embedded with viral proteins.

• The Viral Capsid:

  • Protects and packages the genome.

  • Accounts for the bulk of a virion's mass.

  • Constructed from subunits called capsomeres.

  • Helical Capsids: Resemble a hollow tube (e.g., Tobacco Mosaic Virus, Ebola virus).

  • Icosahedral Capsids: Resemble three-dimensional polygons (e.g., Human Rhinovirus HRV14, Adenovirus).

  • Complex Capsids: Structures that deviate from helical or icosahedral forms (e.g., Variola virus, Bacteriophages).

• Bacteriophages (Phages):

  • Viruses that infect bacteria.

  • Often exhibit complex capsid structures (icosahedral heads associated with additional structures like tails/fibers) to inject their genome into target cells.

Envelopes and Spikes (Peplomers)

• Enveloped Viruses:

  • Possess a lipid-based envelope surrounding the capsid.

  • Arise from budding off the host cell, taking a portion of the host cell membrane with them.

  • Examples: SARS-CoV-2, Human Immunodeficiency Virus (HIV), Ebola virus.

• Naked (Nonenveloped) Viruses:

  • Lack a lipid envelope.

  • Arise from lysing (bursting) the host cell.

  • Examples: Adenovirus, Poliovirus, Papillomavirus (causes plantar warts), Hepatitis A virus.

  • Note: Bacteriophages lyse host cells and are therefore always naked.

• Spikes (Peplomers):

  • Glycoprotein extensions used for attachment and entry into host cells.

  • They bind only to specific factors on a host cell.

  • SARS-CoV-2: Uses the spike glycoprotein on its envelope to bind to the angiotensin-converting enzyme 2 (ACE2) receptor on human cells.

  • Influenza A Spikes:

    1. Hemagglutinin (HA): Protein spike.

    2. Neuraminidase (NA): Enzyme spike.

Viral Genomes and Replication Strategies

• General Genome Facts:

  • Most viruses have fewer than $300$ genes.

  • Genes encode: capsomere proteins, enzymes for replication, and structural factors.

  • Goal: Force host cell to make viral proteins for virion assembly.

• DNA Viral Genomes:

  • Usually double-stranded (dsDNA) but can be single-stranded (ssDNA).

  • Can be circular or linear.

  • dsDNA Viruses: Viral DNA is transcribed by host RNA polymerases into mRNA, which is translated into protein. Some (like retroviruses) integrate into the host genome.

  • ssDNA Viruses: Must be converted to a double-stranded form before transcription can occur.

• RNA Viral Genomes:

  • Usually single-stranded but can be double-stranded (dsRNA).

  • Can be linear, circular, or segmented.

  • Single-stranded positive RNA (ssRNA+): The genome functions directly as mRNA and is immediately ready for translation by host ribosomes.

  • Single-stranded negative RNA (ssRNA-): The genome is complementary to mRNA. It must be transcribed into mRNA by RNA-dependent RNA polymerases (RdRPs).

  • Retroviruses: The ssRNA+ genome is converted into DNA using the enzyme reverse transcriptase. This DNA typically integrates into the host cell's DNA as a provirus and is then transcribed into mRNA.

  • Double-stranded RNA (dsRNA): Requires RdRPs to transcribe the RNA genome into mRNA.

Viral Evolution and Genomic Change

• Evolutionary Speed: Viruses change faster than living infectious agents due to quick replication times and high virion production.

• Proofreading:

  • DNA polymerases have proofreading capabilities.

  • RNA polymerases lack proofreading, leading to higher mutation rates in RNA viruses.

• Impact of Mutations:

  • Attenuated Strains: Genetic changes that limit infectivity (often used in vaccines).

  • Beneficial Mutations: Can help a virus escape the host immune system, broaden host range, expand tropism (cell/tissue types infected), or increase infectivity.

• Reassortment: Occurs when two different viral strains coinfect a single host cell, leading to new genetic combinations.

• Antigenic Drift vs. Antigenic Shift:

  • Antigenic Drift: A gradual, continuous process of minor mutations (e.g., in HA and NA spikes of Influenza) that leads to subtle changes.

  • Antigenic Shift: A sudden, major genetic reassortment. For example, if human and avian influenza strains coinfect a cell (such as a pig lung cell), they can create a new highly virulent strain. This sets the stage for a pandemic because there is no residual immune protection in the population.

Viral Life Cycles

• Replication Locations:

  • Prokaryotic cells: Bacteriophages replicate only in the cytoplasm.

  • Eukaryotic cells:

    • Most DNA viruses replicate in the nucleus.

    • Exception: Large DNA viruses like poxviruses replicate in the cytoplasm.

    • RNA viruses mostly replicate in the cytoplasm.

• Bacteriophage Cycles:

  • Lytic Cycle: The virulent phage takes over the host cell, reproduces new phages, and destroys the cell via lysis.

  • Lysogenic Cycle: The phage genome enters the cell and integrates into the bacterial chromosome. The integrated genome is called a prophage. Example: Lambda phage.

• Transduction: The process where a bacteriophage transfers bacterial DNA from one bacterium to another.

  • Generalized Transduction

  • Specialized Transduction

Life Cycle of Animal Viruses (Focus on HIV)

• ssDNA Viruses in Animals: Host enzymes synthesize a complementary second strand to create dsDNA, which is then used for replication and transcription.

• Retrovirus (HIV) Lifecycle Steps:

  1. Fusion: HIV fuses to the host-cell surface (gp120 binds to CD4 and coreceptors like CCR5 or CXCR4).

  2. Entry: HIV RNA, reverse transcriptase, integrase, and other viral proteins enter the host cell.

  3. Reverse Transcription: Viral DNA is formed from the RNA genome.

  4. Integration: Viral DNA is transported across the nucleus and integrates into host DNA, forming a provirus.

  5. Transcription/Translation: New viral RNA is used as genomic RNA and to make viral proteins.

  6. Assembly: New viral RNA and proteins move to the cell surface; an immature HIV virion forms.

  7. Maturation: The virus matures when the enzyme protease releases the proteins that form the mature HIV infectious particle.

Clinical Case Reference

• The Case of the Cancerous Kiss: A clinical case study illustrating how viruses and prions can explain specific medical mysteries, often utilized in nursing exam preparations like NCLEX, HESI, and TEAS.