Viruses: Structure, Classification, Multiplication, and Pathogenicity

General Characteristics of Viruses

Obligatory Intracellular Parasites

Viruses are unique infectious agents that require living host cells to multiply. They lack the cellular machinery necessary for independent life and reproduction.

• Contain either DNA or RNA: Viruses possess a single type of nucleic acid, either DNA or RNA, but never both.

• No ribosomes: Viruses cannot synthesize proteins independently.

• No ATP-generating mechanism: Viruses rely on host cells for energy.

• Contain a protein coat: The protein coat, or capsid, protects the viral nucleic acid.

• Some viruses are enclosed by an envelope: This lipid membrane is derived from the host cell.

• Some viruses have spikes: Spikes are glycoproteins that aid in attachment to host cells.

• Host range: Most viruses infect only specific types of cells in one host, determined by attachment sites and cellular factors.

Virion Structure

Components of a Virion

A virion is a complete, infectious virus particle. Its structure is essential for protection and delivery of the viral genome.

• Nucleic acid: DNA or RNA, single- or double-stranded.

• Capsid: Protein shell composed of subunits called capsomeres.

• Envelope: Lipid membrane surrounding some viruses.

• Spikes: Surface projections for attachment.

Virus Morphology

Viruses are classified by their shape and structure:

• Polyhedral: Many-sided, often icosahedral.

• Helical: Rod-shaped, with nucleic acid inside a helical capsid.

• Complex: More elaborate structures, such as bacteriophages.

Polyhedral Viruses

Polyhedral viruses, such as Mastadenovirus, have a capsid with many sides, typically icosahedral.

• Example: Mastadenovirus

Enveloped Helical Viruses

Enveloped helical viruses, such as Influenzavirus, have a helical capsid surrounded by an envelope.

• Example: Influenzavirus

Helical Viruses

Helical viruses, such as Ebola virus, have a cylindrical capsid.

• Example: Ebola virus

Complex Viruses

Complex viruses, such as T-even bacteriophages and Orthopoxvirus, have intricate structures with additional components like tails and fibers.

• Example: T-even bacteriophage, Orthopoxvirus

Taxonomy of Viruses

Classification Principles

Virus taxonomy is based on genetic material, host range, and structural features.

• Family names: End in -viridae

• Genus names: End in -virus

• Viral species: Group sharing genetic information and ecological niche

• Common names: Used for species

• Subspecies: Designated by numbers

Examples of Virus Families

• Herpesviridae: Includes Herpesvirus (HHV-1, HHV-2, HHV-3)

• Retroviridae: Includes Lentivirus (HIV-1, HIV-2)

Isolation, Cultivation, and Identification of Viruses

Growing Viruses

Viruses must be grown in living cells, as they cannot replicate independently.

• Bacteriophages: Form plaques on a lawn of bacteria.

• Animal viruses: Grown in living animals, embryonated eggs, or cell cultures.

• Continuous cell lines: Transformed cells that can be maintained indefinitely.

Viral Multiplication

The Lytic Cycle

The lytic cycle is a process by which bacteriophages replicate and destroy the host cell.

• Attachment: Phage attaches to host cell via tail fibers.

• Penetration: Phage lysozyme opens cell wall; DNA injected.

• Biosynthesis: Production of phage DNA and proteins.

• Maturation: Assembly of phage particles.

• Release: Cell wall breaks, releasing new virions.

The Lysogenic Cycle

In the lysogenic cycle, phage DNA integrates into the host genome and replicates without killing the cell.

• Prophage DNA: Incorporated in host DNA.

• Phage conversion: Host cell acquires new properties.

• Specialized transduction: Transfer of specific bacterial genes by phage.

Transduction by a Bacteriophage

Transduction is the process by which bacterial DNA is transferred from one cell to another by a virus.

• Generalized transduction: Any bacterial gene may be transferred.

• Specialized transduction: Only specific genes are transferred.

Multiplication of Animal Viruses

Steps in Animal Virus Multiplication

Animal viruses follow a series of steps to infect host cells:

• Attachment: Viruses attach to cell membrane.

• Penetration: Entry by endocytosis or fusion.

• Uncoating: Viral or host enzymes remove capsid.

• Biosynthesis: Production of nucleic acid and proteins.

• Maturation: Assembly of nucleic acid and capsid proteins.

• Release: By budding (enveloped viruses) or rupture.

Replication of DNA-Containing Animal Viruses

DNA viruses replicate in the host cell nucleus and follow a specific sequence of events.

• Attachment, Entry, and Uncoating

• Biosynthesis: Early and late transcription/translation

• Maturation and Release

Replication of RNA-Containing Animal Viruses

RNA viruses replicate in the cytoplasm and use viral RNA-dependent RNA polymerase.

• + strand (sense): Acts as mRNA

• - strand (antisense): Must be transcribed to + strand

• dsRNA: Double-stranded RNA viruses

Multiplication and Inheritance of Retroviridae

Retroviruses use reverse transcriptase to produce DNA from RNA, which integrates into the host genome.

• Reverse transcriptase: Enzyme that synthesizes DNA from RNA

• Integration: Viral DNA becomes a provirus in host chromosome

• Transcription: Provirus DNA transcribed to produce new viral genomes and proteins

• Release: Virus buds from host cell, acquiring envelope

Latent and Persistent Viral Infections

Latent and Persistent/Chronic Infections

Some viruses remain dormant in host cells, while others cause prolonged disease.

• Latent infection: Virus remains in asymptomatic host cell for long periods (e.g., cold sores, shingles)

• Persistent infection: Disease process occurs over a long period, often fatal (e.g., subacute sclerosing panencephalitis)

Viruses and Cancer

Oncogenic Viruses

Oncogenic viruses can cause cancer by integrating their genetic material into host DNA and transforming normal cells.

• Activated oncogenes: Transform normal cells into cancerous cells

• Transformed cells: Increased growth, loss of contact inhibition, tumor-specific antigens

• Integration: Genetic material of oncogenic viruses becomes part of host DNA

• Oncogenic DNA viruses: Adenoviridae, Herpesviridae, Poxviridae, Papovaviridae, Hepadnaviridae

• Oncogenic RNA viruses: Retroviridae (HTLV-1, HTLV-2)

Virus Families That Affect Humans

Major Virus Families

• Adenoviridae: Double-stranded DNA, nonenveloped; respiratory infections, tumors

• Papovaviridae: Double-stranded DNA, nonenveloped; papillomavirus, some serotypes cause cancer

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• Poxviridae: Double-stranded DNA, enveloped; smallpox, cowpox

• Herpesviridae: Double-stranded DNA, enveloped; includes HHV-1 to HHV-8, some remain latent

• Hepadnaviridae: Double-stranded DNA, enveloped; hepatitis B virus, uses reverse transcriptase

• Picornaviridae: Single-stranded RNA, + strand, nonenveloped; enterovirus, rhinovirus, hepatitis A

• Caliciviridae: Single-stranded RNA, + strand, nonenveloped; hepatitis E, norovirus

• Flaviviridae: Single-stranded RNA, + strand, enveloped; arboviruses, hepatitis C

• Rhabdoviridae: Single-stranded RNA, − strand; rabies virus

• Filoviridae: Single-stranded RNA, − strand; Ebola, Marburg viruses

• Orthomyxoviridae: Single-stranded RNA, − strand, multiple strands; influenza viruses

• Retroviridae: Single-stranded RNA, two strands; HIV, oncogenic viruses

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Antigenic Shift and Independent Assortment

Antigenic Shift in Influenza Virus

Antigenic shift is the process by which two different strains of a virus combine to form a new subtype with mixed surface antigens.

• Mechanism: Independent assortment of viral genome segments

• Example: 2009 H1N1 pandemic resulted from reassortment of human, avian, and swine influenza viruses

Prions

Proteinaceous Infectious Particles

Prions are infectious proteins that cause neurodegenerative diseases.

• Inherited and transmissible: By ingestion, transplant, and surgical instruments

• Spongiform encephalopathies: Includes sheep scrapie, Creutzfeldt-Jakob disease, mad cow disease

• Cellular Prion Protein (PrPC): Normal protein on cell surface

• Scrapie Protein (PrPSc): Abnormal form, accumulates in brain cells, forming plaques

Smallpox

Smallpox Virus and Disease

Smallpox, caused by Variola virus, was a deadly disease eradicated by vaccination.

• Symptoms: Maculopapular rash, raised fluid-filled blisters

• Eradication: Last natural outbreak in the US in 1949; declared eliminated in 1980

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