Comprehensive Study Notes on Virion Structure, Life Cycles, and Replication

Anatomy and basic structure of a fully formed virion

• A virion is a fully formed viral particle that is mature enough to infect a new host cell.
• Genetic material: viruses contain either DNA or RNA, but never both; they are categorized as either DNA viruses or RNA viruses.
• Nucleic acid is enclosed by a capsid, forming the nucleocapsid; the capsid surrounds and protects the genetic material.
• Capsid structure:
  • The capsid is made up of individual proteins called capsomeres.
  • Capsomeres assemble to form the capsid.
  • The capsid’s shape and arrangement differ among virus types.
• Spikes (glycoprotein spikes): many viruses have spikes used for attachment to host cells and for entry; they are composed of glycoproteins.
• Enveloped vs non-enveloped (naked) virions:
  • Enveloped virions have a viral envelope; non-enveloped virions do not.
  • The envelope is a phospholipid bilayer acquired from the host cell membrane during viral budding.
  • The envelope contains viral proteins and host-derived lipids; envelope presence influences entry and release mechanisms.
• Viral entry and envelope acquisition:
  • Enveloped viruses gain their envelope from the host cell plasma membrane during budding; the host cell membrane forms the viral envelope around the capsid as virions exit.
  • Some viruses are non-enveloped and do not acquire a host-derived envelope.
• Viroids vs viruses vs prions (overview):
  • Viroids: short circular RNA molecules that can self-replicate and hijack host machinery; infect plants; lack a protective protein coat.
  • Viruses: infectious particles with nucleic acid (DNA or RNA) and a protein coat (capsid), with or without a lipid envelope.
  • Prions: infectious protein particles without nucleic acids; consist of misfolded forms of normal host brain proteins; cause neurodegenerative diseases; highly resistant to destruction.
• Transmission context:
  • Transmission between animals can occur when contaminated tissue is used as feed for living animals.

Viroids

• Viroids are short circular RNA molecules.
• They replicate and can hijack host cellular machinery to replicate their RNA, despite lacking a protein coat.
• Viroids are primarily plant pathogens.

Prions

• Prions are proteinaceous infectious particles with no nucleic acid.
• A prion is an abnormally folded form of a normally occurring brain cell protein.
• The misfolded prion can induce misfolding of other normal proteins, leading to harmful aggregation and cell death.
• Tissue and disease implications:
  • Prion diseases are transmissible spongiform encephalopathies (TSEs) characterized by spongy vacuoles in cortical and cerebellar brain tissue.
  • Early symptoms can include memory loss, behavioral changes, lack of coordination, and visual disturbances; progression leads to mental deterioration, motor symptoms, and fatal outcomes.
  • Prions resist destruction by many chemical agents and survive extreme temperatures.
• Transmission risks include hereditary mechanisms or contact with contaminated tissue.

Bacteriophage life cycle (phage replication in bacteria)

• Attachment and entry:

  • Complementary receptor on the bacterial cell serves as the attachment site for the phage.
  • The phage docks to the bacterial receptor, forming a weak chemical bond.
  • Penetration involves the phage tail releasing an enzyme that degrades a portion of the bacterial cell wall.
  • The phage DNA passes through the tail core from the phage head into the bacterial cytoplasm; the capsid remains attached to the outside of the cell.

• Biosynthesis and replication:

  • Once inside the cytoplasm, host cell protein synthesis is interrupted by the virus.
  • The phage genome is integrated into the host genome or expressed to produce viral components, hijacking host machinery for transcription and translation.
  • Early phage genes are expressed to transcribe DNA and initiate replication of the phage genome.
  • Other phage-encoded proteins replicate the phage genome and produce capsid and tail components.

• Assembly and maturation:

  • Capsomeres self-assemble into capsids and package the phage genome in a stepwise, factory-like process.
  • Late genes express an enzyme that lyses the host cell, releasing mature phage; this lysis event is called a burst, and the number of phage released is the burst size.

• Release:

  • Release of phage particles into the environment to infect new cells.

• Lytic vs temperate (lysogenic) phages:

  • Virulent phages reproduce exclusively by the lytic cycle (lysis and release).
  • Temperate phages can also undergo lysogeny, integrating their genome into the host genome (prophage) and remaining dormant alongside the host’s genome.

• Lysogeny and prophage:

  • Integration occurs via site-specific recombination, where phage DNA aligns with the host genome and exchanges genetic material.
  • The integrated phage genome is called a prophage and is replicated with the host genome during cell division.
  • Lysogeny can be spontaneous or induced by environmental cues; temperate phages may reactivate and enter the lytic cycle.

• Induction and environmental triggers:

  • Conditions that threaten host cell survival (e.g., UV-induced DNA damage) can trigger the prophage to excise from the genome and enter the lytic cycle.
  • In humans and animals, latent infections (e.g., herpes) can be reactivated by stress, mirroring phage induction mechanisms.

• Lysogeny in other systems:

  • HIV and other human/animal viruses also employ integration into the host genome as a provirus, similar to prophage in bacteria.

Transduction (gene transfer by phages)

• During exit from lysogeny or latent growth of animal viruses, some phages can acquire host genes and transfer them to another host cell (transduction).
• Generalized transduction: a phage carrying random host DNA can infect a new cell and transfer host genes.
• Specialized transduction (implied by discussion of entire genome replacement): in some cases, host DNA adjacent to the prophage genome is packaged and transferred.

Retroviruses and integration (example: HIV)

• Entry and reverse transcription:
  • An enveloped retrovirus binds to the host cell and fuses its envelope with the cell membrane, releasing its core into the cytoplasm.
  • The two RNA genomes are reverse-transcribed by reverse transcriptase into double-stranded DNA.
  • The DNA is integrated into the host genome as a provirus at a random position.
• Transcription and replication:
  • The host cell machinery transcribes the proviral DNA into RNA, which serves as both genome and mRNA for protein production.
  • Some RNA copies function as mRNA for translation; full-length transcripts are packaged into new virions.
• Enveloped virus assembly and release:
  • Enveloped viruses like HIV bud from the host cell, acquiring their envelope from the host membrane.
  • The process of budding results in an enveloped virion; enveloped viruses can cause persistent infections because budding may not immediately kill the host cell.

Enveloped vs non-enveloped entry mechanisms (detail on entry)

• Two mechanisms for enveloped viruses to enter host cells:
  1) Direct fusion at the plasma membrane: envelope proteins interact with host receptors, the envelope fuses with the plasma membrane, and the nucleocapsid is released into the cytoplasm; nucleic acid separates from the capsid.
  2) Receptor-mediated endocytosis: the virus binds to receptors, is internalized in a vesicle, the envelope fuses with the vesicle membrane, releasing the nucleocapsid into the cytoplasm; capsid proteins are removed to release viral nucleic acid.
• Naked (non-enveloped) virions entry:
  • Enter by endocytosis; after endocytosis, nucleic acid is released from the endocytic vesicle.
• Uncoating:
  • Uncoating is the crucial step where the viral nucleic acid is separated from the protein coat.

Viral replication cycles: common phases

• General stages shared across many viruses:
  • Host recognition and attachment: virus binds to specific surface receptors on the host cell.
  • Genome entry: viral genome enters the host cell and gains access to the cellular machinery.
  • Biosynthesis/assembly: viral components are synthesized and assembled into progeny virions.
  • Exit and transmission: virions exit the host cell to infect new cells.

Animal virus replication specifics

• Attachment: animal viruses attach via receptor proteins; envelope spikes often mediate attachment in enveloped viruses.
• Entry: enveloped viruses can fuse or enter via endocytosis; non-enveloped viruses typically enter via receptor-mediated endocytosis.
• Uncoating: separation of genomic material from the protein coat, enabling replication.
• Replication strategies by genome type:
  • DNA viruses: generally replicate DNA in the nucleus of the host cell.
  • RNA viruses: generally replicate in the host cytoplasm.
  • Retroviruses (e.g., HIV): use reverse transcriptase to convert RNA to DNA, integrate into the host genome as a provirus, then use host machinery to transcribe and translate.
• Enveloped virus architecture:
  • The capsid of many animal viruses is enclosed in an envelope containing host- or virus-derived lipids, proteins, and carbohydrates.
  • The envelope forms around the capsid as the virus buds from the host cell.
• Release mechanisms:
  • Enveloped viruses typically release by budding, which may preserve the host cell.
  • Non-enveloped viruses typically exit by cell lysis, which destroys the host cell.

Key terms and concepts to remember

• Burst size: the number of virions released per lysed host cell (described in bursts during lytic cycles).
• Prophage: integrated phage genome within a bacterial host genome during lysogeny.
• Lysogeny: phage genome remains integrated with the host genome and is replicated with host DNA.
• Provirus: integrated viral genome within a host genome (e.g., HIV) that can be transcribed and replicated with the host.
• Site-specific recombination: the enzyme-mediated process by which phage DNA integrates into host DNA during lysogeny.
• Temperate phage: a phage capable of both lytic and lysogenic cycles.
• Virulent phage: phage that reproduces exclusively via the lytic cycle.
• Transduction: transfer of host genes between bacteria via phage infection.
• Reverse transcriptase: enzyme used by retroviruses to convert RNA into DNA.
• Prokaryotic vs eukaryotic host context: bacteria host phages; animal viruses infect eukaryotic cells (humans/animals).
• Transmission routes and implications: prions resist chemical destruction and heating; prion diseases are fatal; viroids infect plants; different implications for public health and agriculture.

Relevance and implications

• Understanding the structure of virions (capsid, spikes, envelope) informs how viruses attach, enter, and exit host cells, and why certain viruses are susceptible to detergents or disinfectants that disrupt lipid envelopes.
• The distinction between enveloped and non-enveloped viruses affects stability, transmission routes, and immune recognition.
• Knowledge of lytic vs lysogenic cycles explains phage therapy potential and how bacteria evolve resistance through lysogeny and transduction.
• Retroviral replication (reverse transcription and provirus integration) highlights why some viruses establish permanent infections and why antiretroviral therapies target steps like reverse transcription and integration.
• Prions and viroids emphasize non-traditional infectious agents and the challenges of deactivation and disease containment in public health and agriculture.
• The concept of burst size and timing of lysis vs persistence influences understanding of viral load dynamics and disease progression.

Connections to broader foundational principles

• Virus-host interactions illustrate fundamental principles of molecular recognition (receptor–ligand binding) and membrane biology (lipid bilayers, budding, fusion).
• The central dogma and viral deviations: reverse transcription in retroviruses shows RNA-to-DNA flow, expanding the classic DNA-to-RNA-to-protein paradigm to include RNA genomes and reverse transcription.
• Evolutionary arms race: host receptors and viral attachment proteins co-evolve; environmental stresses can trigger transitions between latent and active viral states in temperate phages and latent human viruses (e.g., herpes).
• Public health relevance: understanding prions, viroids, and transduction informs biosafety, food safety, and disease control strategies.

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