GENERAL CHARACTERISTICS AND STRUCTURE OF VIRUSES

GENERAL CHARACTERISTICS AND STRUCTURE OF VIRUSES

Lecture Objectives:

By the end of this instructional period, students will be able to:

• Explain why viruses are classified as acellular, obligate intracellular parasites.
• Describe and label the essential components of a virus.
• Describe the key differences between virulent and temperate bacteriophages.
• Outline and describe the stages of the lytic and lysogenic cycle of bacteriophage replication.

What is a Virus?

Viruses are the smallest infectious agents whose genomes consist of deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) and are absolutely dependent on living cells for their replication.

Are Viruses Living or Non-Living?

Why Viruses Are Considered "Non-Living":

• No Cell Structure: Lack cellular structure; consist of genetic material (DNA or RNA) encased in a protein shell (capsid), sometimes with a lipid envelope.
• Metabolic Deficiency: Incapable of generating their own energy (ATP) or synthesizing proteins due to the absence of cellular organelles like ribosomes and mitochondria.
• Lack of Autonomous Reproduction: Cannot divide or proliferate independently; are "obligate intracellular parasites" that hijack host cells to create new particles.
• Inert Outside a Host: Exhibit no responsiveness, proliferation, or homeostasis outside a host. Many can be crystallized, a property of non-living matter.

Why Viruses Are Considered "Living":

• Genetic Material: Possess nucleic acids (DNA or RNA), a common trait among all living species.
• Replication: Can reproduce and proliferate, albeit by commandeering a host cell.
• Evolution and Adaptation: Undergo mutations and evolve over time, adapting to evade immune systems (e.g., influenza).
• Complex Structure: Have an organized protein covering (capsid) and sometimes a lipid envelope, functioning as organized entities.

General Characteristics and Properties of Viruses:

• Size: Measured in nanometres (20 nm to 300 nm). They are too small to be seen with a light microscope and require an electron microscope.
• Lack of Organelles: Lack cellular organization, cytoplasm, cell wall, and cellular organelles.
• Genetic Material: Contain either DNA or RNA, but never both. Genomes are relatively small (2 kbp to 200 kbp).
• Obligate Intracellular Parasites: Cannot replicate or carry out metabolic processes outside a host cell; entirely dependent on host machinery (ribosomes, ATP, enzymes).
• Replication Method: Do not multiply by binary fission. Reproduce through a complex process of directed protein synthesis and nucleic acid production within a host.
• Host Specificity: Highly selective, usually infecting specific host organisms or cell types. Determined by interaction between viral surface molecules and host cell receptors.
• Host Range: Infect all life forms (animals, plants, microorganisms). Viruses infecting bacteria are called bacteriophages; those infecting fungi are mycophages.

Structure of Viruses:

• A virus particle, or virion, consists of nucleic acid (DNA or RNA) enclosed by a protein coat called a capsid.
• The nucleocapsid can be naked or enclosed by a membrane called an envelope.

Viral Genome:

• Contains genes necessary to direct infected cells to synthesize viral components and replication enzymes.
• Consists of four possible nucleic acid types:
  • Single-stranded (ss) DNA
  • Double-stranded (ds) DNA
  • Single-stranded (ss) RNA (can be positive or negative polarity)
  • Double-stranded (ds) RNA
• Single-stranded viral RNA genomes:
  • Positive polarity (messenger RNA sense): Can serve as a template for protein synthesis.
  • Negative polarity (antisense): Complementary to mRNA, cannot be directly used as a template for protein synthesis.
• Viral nucleic acid may be linear or circular. (No known circular dsRNA genomes).

Capsid:

• The capsid is a protective outer shell surrounding the viral nucleic acid, made of subunits called capsomeres, which are composed of a protomere.
• The structure of the nucleic acid genome and the capsid proteins is called the nucleocapsid.
• The capsid serves to:
  • Protect the viral genome from harmful environmental factors (UV light, desiccation, acids, degradative enzymes).
  • Mediate attachment to specific receptors on the host cell surface, determining species- and organ-specificity.
  • Stimulate the production of neutralizing antibodies and activate cytotoxic T cells.

Capsid Symmetry:

• Capsomeres are arranged symmetrically into specific shapes: icosahedral and helical.
• Helical Capsid:
  • Composed of a single type of capsomer stacked around a central axis to form a helical structure, which may have a central cavity.
  • Most helical viruses are enveloped and all are RNA viruses.
  • Example: Tobacco mosaic virus (TMV) (RNA virus with 2130 identical capsomeres in a helix).
• Icosahedral Capsid:
  • A regular three-dimensional shape with 20 triangular faces and 12 points/corners. Capsomeres form equilateral triangles on each face.
  • Most stable and found in human-pathogenic viruses.
  • Examples: Adenovirus, Picornavirus, Papovavirus, Herpes virus.
• Complex Viruses:
  • Composed of several parts, each with distinct shapes and symmetries.
  • Most structurally complex viruses are found among bacterial viruses (bacteriophages), which have icosahedral heads and helical tails, and the poxvirus.

Envelope:

• A lipid bilayer membrane that some viruses have outside their capsids.
• Derived from host cell membranes during viral release, but virus-specific proteins replace host proteins.
• In enveloped viruses, capsomeres form structures called "spikes" or "peplomers" that stick out from the lipid bilayer.
• A virus without an envelope is called a non-enveloped virus, nucleocapsid, or naked virus.
• Naked viruses exhibit greater resistance to environmental changes because their genetic material is protected solely by a sturdy capsid.
• Environmental factors that can damage the envelope include: elevated temperatures, freezing temperatures, pH below 6 or above 8, lipid solvents, and certain chemical disinfectants (chlorine, hydrogen peroxide, phenol).

Replication of Viruses:

• Viral replication cycles follow a general sequence but vary depending on viral structure and host cell nature.
• The life cycle of bacteriophages serves as an excellent model for understanding viral replication.
• The most studied bacteriophage is the T-even bacteriophage, which infects *E. coli*.
• Bacteriophages can replicate through either a lytic or a lysogenic cycle.
• They are categorized as either virulent phages (lytic cycle) or temperate phages (lytic or lysogenic cycle).

Lytic Replication of Bacteriophage (Virulent Phages):

A virulent bacteriophage takes over the host cell, synthesizes new phage components, assembles new phages, and ultimately destroys the host cell to release its progeny.

The lytic cycle has five distinct stages:

1. Attachment (Adsorption):
   • Phage interacts with specific bacterial surface receptors (e.g., lipopolysaccharides or outer membrane proteins) using its tail fibers.
   • This interaction determines host specificity.
2. Penetration (Entry):
   • Bacteriophages use an enzyme (lysozyme) in their tails to break down the bacterial cell wall.
   • They inject their DNA (nucleic acid) into the bacterium, while the phage head (capsid) and other components typically stay outside.
3. Replication (Biosynthesis):
   • Viral DNA produces endonucleases that degrade the host bacterium's chromosome.
   • The viral genome becomes the primary template, hijacking the host cell's machinery for phage DNA and protein synthesis.
4. Assembly (Maturation):
   • Newly synthesized viral components (genomes and proteins) self-assemble into complete new viral particles (virions).
   • Non-enveloped viruses are fully developed within the host cell; enveloped viruses acquire their envelope from the plasma membrane during release.
5. Release (Lysis):
   • The final stage where newly assembled mature viruses burst out of the host cell.
   • Phage-encoded proteins disrupt the bacterial cell wall, releasing progeny viruses into the environment.
   • This process, called lysis, results in the death of the host cell.

Lysogenic Replication of Bacteriophage (Temperate Phages):

In a lysogenic cycle, the phage genome enters the cell through attachment and penetration but integrates into the host genome rather than immediately hijacking the cell for rapid replication and lysis.

• Attachment and Penetration: Similar to the lytic cycle; phage attaches and injects its DNA.
• Integration (Prophage Formation):
  • The temperate phage's DNA integrates into the bacterial chromosome at a specific site.
  • The integrated phage genome is called a prophage.
  • The host cell harboring a prophage is known as a lysogen.
• Replication with Host (Cellular Propagation):
  • The prophage is typically latent or inactive, not producing new virions.
  • As the lysogenic bacterium replicates its chromosome, the prophage genome is passively replicated along with the host genome and passed on to all new daughter cells.
• Lysogenic Conversion (Phage Conversion):
  • The presence of a prophage can alter the phenotype (observable characteristics) of the host bacterium because the prophage carries additional genes.
  • Examples: *Vibrio cholerae* and *Clostridium botulinum* gain virulence when their prophages carrying toxin genes are present.
  • The lambda (λ) phage is a classic example of a temperate phage capable of lysogeny.
• Induction:
  • The prophage can persist for many generations.
  • Under certain environmental stressors (e.g., starvation, UV radiation, toxic chemicals), the prophage can be induced.
  • Induction results in the excision (cutting out) of the viral genome from the host chromosome, becoming an independent, circular molecule.
• Switch to the Lytic Cycle: After induction and excision, the temperate phage can then enter a lytic cycle, leading to the production and release of new phages, which can infect other cells.

Difference between the Lytic and Lysogenic Cycles:

• Viral Activity:
  • Lytic: Active and immediate (virulent).
  • Lysogenic: Dormant (lysogeny).
• Host Cell Fate:
  • Lytic: Destroyed; cell bursts (lyses) to release virions.
  • Lysogenic: Survives; cell continues to divide and function normally.
• Viral DNA:
  • Lytic: Remains separate from the host's DNA.
  • Lysogenic: Integrated directly into the host genome as a prophage.
• Reproduction Speed:
  • Lytic: Rapidly hijacks host machinery to mass-produce viruses immediately.
  • Lysogenic: Slow; viral DNA is quietly copied every time the host cell divides.
• Replication:
  • Lytic: Viral particles are synthesized and assembled independently of host DNA.
  • Lysogenic: The viral DNA is copied automatically every time the host cell divides.
• Transition Triggers:
  • Lytic: It is immediately active.
  • Lysogenic: Stress or environmental changes can cause the virus to exit lysogeny and enter the lytic cycle.

Atypical Virus-Like Particles:

Viroids:

• Small, infectious, circular, single-stranded RNA particles that cause disease in plants.
• Consist solely of an RNA molecule without a protein coat (capsid) or envelope.
• Replicate by hijacking host reproductive machinery.
• Smallest known pathogens (2 nm wide, 40–130 nm long).
• Cause diseases like potato spindle tuber disease.
• Have two structural types: rod-like and multibranched.
• Infect only plants, not humans.

Prions:

• Infectious proteins whose extracellular forms contain no nucleic acid and no envelope.
• Discovered by Stanley Prusiner in 1982.
• Normal prions contain 200–250 amino acids twisted into three helical coils.
• Cause various forms of transmissible spongiform encephalopathy (TSE) in humans and animals.
• TSEs affect the brain and nervous system, causing brain tissue to become sponge-like, killing brain cells, forming holes, leading to brain damage, loss of motor coordination, and dementia.
• No cure; diseases progress rapidly to death.
• Can be transmitted between animals and from animals to humans by eating contaminated meat.

Pseudoviruses:

• Artificially engineered viral particles that mimic the structure and entry mechanism of a real virus.
• Lack the pathogenic genetic material required to replicate.
• Contain host DNA instead of viral DNA; they infect the host cell but don't replicate.
• Used for mechanistic investigation of viral infection.

Defective Viruses:

• Contain viral nucleic acid and proteins but cannot replicate without a helper virus.
• Satellite viruses are a type of defective virus for which no intact version exists; they entirely rely on helper viruses for replication.
• Example: The Delta agent (Hepatitis Delta virus) requires the presence of the hepatitis B virus to replicate.