Viruses as Pathogens

General Characteristics of Viruses

Viruses are minuscule, acellular infectious agents that can infect humans, animals, plants, and bacteria. They are responsible for many diseases and possess unique structural and functional properties.

• Structure: Viruses lack cytoplasmic membrane, cytosol, and organelles. They do not carry out metabolic pathways, grow, or respond to the environment, and cannot reproduce independently.

• States: Viruses exist in two states: extracellular (virion) and intracellular (nucleic acid only).

• Virion: The extracellular form consists of a protein coat (capsid) surrounding nucleic acid (forming the nucleocapsid). Some virions have a phospholipid envelope derived from the host cell.

• Host Specificity: Determined by recognition of receptor proteins; some viruses are generalists infecting multiple cell types or hosts.

Defining Structural and Functional Characteristics

• Genetic Material: Viruses contain either DNA or RNA, but never both. Their genomes may be single-stranded (ss) or double-stranded (ds), linear, segmented, or circular. Hepadnaviruses may have both ds and ss regions.

• Shapes: Viruses are classified by virion shape: helical, polyhedral, or complex.

• Envelope: The viral envelope is acquired from the host cell and consists of a phospholipid bilayer and proteins, including virally coded glycoproteins (spikes) important for host recognition.

Viral Lifecycle and Replication

Bacteriophage Replication

Bacteriophages are viruses that infect bacteria. Their replication can follow two main cycles: lytic and lysogenic.

• Lytic Cycle: Results in death and lysis of the host cell. The five stages are:

  • Attachment

  • Entry

  • Synthesis

  • Assembly

  • Release

• Lysogenic Cycle: Modified replication where the phage genome integrates into the host genome as a prophage. The host cell reproduces normally for generations before lysis. Lysogenic conversion occurs when phages carry genes that alter the phenotype of the bacterium.

Comparison of Lytic and Lysogenic Cycles

Replication of Animal Viruses

Animal viruses follow similar replication pathways as bacteriophages, with differences due to the presence of an envelope, the eukaryotic nature of animal cells, and the lack of a cell wall.

• Attachment: Binding of viral glycoprotein spikes on the capsid or envelope to host cell receptors.

• Entry and Uncoating: Viruses enter host cells by direct penetration, endocytosis, or membrane fusion. Uncoating releases the viral genome.

• Synthesis: Strategy depends on the type of nucleic acid:

  • DNA Viruses: Often enter the nucleus; replication similar to cellular DNA replication.

  • RNA Viruses: Replicate in the cytoplasm. Positive-sense (+) RNA acts as mRNA; negative-sense (–) RNA must be transcribed to mRNA. Four types: +ssRNA, –ssRNA, dsRNA, and retroviruses.

• Assembly and Release: Most DNA viruses assemble in the nucleus; most RNA viruses assemble in the cytoplasm. Enveloped viruses are released by budding (can cause persistent infections), while naked viruses are released by exocytosis or lysis.

• Latency: Some animal viruses remain dormant as latent viruses or proviruses. Incorporation into host DNA is permanent and may last for years without activity.

Viral Genomes

Types and Organization

Viral genomes are highly variable and are a primary means of classification.

• DNA Viruses: May be single-stranded (ssDNA) or double-stranded (dsDNA), linear or circular.

• RNA Viruses: May be single-stranded (ssRNA) or double-stranded (dsRNA), segmented or non-segmented.

• Retroviruses: Possess +ssRNA and replicate via a DNA intermediate.

Example: Hepadnaviruses have both ds and ss regions in their genome.

Modes of Entry and Exit from Mammalian Cells

Entry Mechanisms

• Direct Penetration: Viral capsid attaches and injects nucleic acid into the host cell.

• Endocytosis: Host cell engulfs the virus in a vesicle.

• Membrane Fusion: Viral envelope fuses with the host cell membrane, releasing the capsid into the cytoplasm.

Exit Mechanisms

• Budding: Enveloped viruses acquire their envelope from the host cell membrane during release, often resulting in persistent infections.

• Exocytosis or Lysis: Naked viruses are released by host cell rupture or exocytosis.

Viral Culture Methods

Comparison of Culture Techniques

• Bacterial Viruses (Bacteriophages): Cultured using bacterial lawns on agar plates; plaques indicate viral infection.

• Animal Viruses: Cultured in living animals, embryonated eggs, or cell cultures. Cell cultures allow observation of cytopathic effects.

• Plant Viruses: Cultured in whole plants or plant cell cultures.

Other Infectious Agents

Viroids

Viroids are extremely small, circular pieces of ssRNA that infect plants. They do not code for proteins and cause disease by interfering with plant RNA.

Prions

Prions are proteinaceous infectious agents. Normal cellular PrP has α-helices, while disease-causing prion PrP has β-pleated sheets. Prions induce misfolding of normal PrP and are resistant to standard autoclaving.

Virulence Factors and Immune Evasion

Attachment and Entry

• Attachment to specific cell types determines disease type and severity.

• Surface proteins are key targets for immune recognition.

Genetic Variation and Immune Evasion

• Antigenic Drift: Frequent mutations in RNA viruses due to lack of proofreading.

• Antigenic Shift: Recombination of viral genomes in animal hosts (e.g., influenza).

• Some viruses downregulate MHC I or inhibit interferon release to evade immune detection.

Oncogenic Viruses

• Some viruses carry oncogenes or promote host oncogenes, interfering with tumor repression and causing cancers such as Burkitt's lymphoma, Hodgkin's disease, Kaposi's sarcoma, and cervical cancer.

Additional info: The notes infer standard viral replication steps and culture methods based on common microbiology curriculum.