Viruses: Structure, Replication, and Viral Diseases

Viruses: Introduction and Classification

Overview of Viruses, Viroids, and Prions

Viruses are acellular infectious agents that require host cells for replication. They are distinct from living organisms due to their inability to carry out independent metabolic processes.

• Virion: The complete, infectious form of a virus outside a host cell, consisting of a nucleic acid core surrounded by a proteinaceous capsid.

• Virus: Tiny acellular agent with either DNA or RNA as its genome; lacks cellular structure.

• Prion: Proteinaceous infectious particle lacking nucleic acids; replicates by converting normal proteins into abnormal forms, causing diseases such as Creutzfeldt-Jakob disease.

• Viroid: Naked RNA molecule that infects plants; does not encode proteins.

Are Viruses Alive?

Viruses are not considered living organisms because they cannot independently perform life processes.

• Not made of cells (acellular)

• Cannot reproduce or grow/divide independently

• Do not perform metabolism or synthesize proteins

Structural Characteristics of Viruses

Basic Components

Viruses are composed of nucleic acids (DNA or RNA), proteins, and sometimes a lipid envelope.

• Nucleic Acid: The genetic material, either DNA or RNA, single or double stranded.

• Capsid: Protein coat made of subunits called capsomeres; provides protection and attachment to host cells.

• Envelope: Lipid membrane derived from host cell, containing viral glycoproteins; present in some viruses.

• Spikes: Protein projections from the capsid or envelope, involved in host cell recognition and attachment.

Formula: $ext{Nucleic acid} + ext{Capsid} = ext{Nucleocapsid}$

Virus Envelope

The envelope is acquired from the host cell during viral replication or release and is composed of phospholipids and viral proteins (glycoproteins).

• Envelope proteins and glycoproteins play a key role in host recognition and penetration.

• Spikes are large proteins on the envelope surface that facilitate attachment.

Classification: Families of Viruses That Affect Humans

Major Virus Families

Viruses are classified based on their nucleic acid type, structure, and replication strategy. Below is a summary table of important human virus families:

Characteristic	Viral Family	Important Genus
Single Stranded DNA	Parvoviridae	Parvovirus B19
Double Stranded DNA	Herpesviridae	Herpes simplex virus
Double Stranded DNA	Poxviridae	Variola virus (smallpox)
Single Stranded RNA (+)	Picornaviridae	Poliovirus, Rhinovirus
Single Stranded RNA (-)	Orthomyxoviridae	Influenza virus
Double Stranded RNA	Reoviridae	Rotavirus
Retrovirus (ssRNA-RT)	Retroviridae	HIV

Virus Structure Types

Capsid Types

• Helical Viruses: Hollow, cylindrical capsid (e.g., Ebola virus).

• Polyhedral Viruses: Capsids with geometrical sides (e.g., Adenovirus).

• Complex Viruses: Complicated structures, such as bacteriophages with additional components (e.g., T4 bacteriophage).

Enveloped Virus Structures

• Envelope Helical Viruses: Helical capsid surrounded by an envelope (e.g., Influenza virus).

• Envelope Polyhedral Viruses: Polyhedral capsid with an envelope (e.g., Herpes simplex virus).

Virus Sizes

Viruses are much smaller than cells, typically ranging from 20 nm to 300 nm in diameter.

• Poliovirus: ~30 nm

• Bacteriophage T4: ~225 nm

• Smallpox virus: ~200 nm x 300 nm

• Red blood cell: ~10,000 nm diameter (for comparison)

Virus Replication Cycle

General Steps in Animal Virus Replication

Animal viruses replicate through a series of coordinated steps:

1. Attachment: Virus binds specifically to host cell receptors via capsid proteins or envelope glycoproteins.

2. Penetration (Entry): Virus enters the host cell by direct penetration, membrane fusion, or endocytosis.

3. Biosynthesis: Viral genome is replicated and viral proteins are synthesized using host cell machinery.

4. Assembly and Maturation: Viral components are assembled into new virions.

5. Release (Exit): New virions exit the host cell by lysis, budding, or exocytosis.

Attachment

• Specific interaction between viral surface proteins (spikes) and host cell receptors.

• Capsomeres on non-enveloped viruses; glycoproteins on enveloped viruses.

• Host specificity is determined by receptor compatibility.

Penetration

• Direct Penetration: Naked viruses inject their genome into the host cell.

• Membrane Fusion: Enveloped viruses fuse with host cell membrane, releasing genome.

• Endocytosis: Host cell engulfs virus in a vesicle; viral genome is released inside the cell.

Biosynthesis

Viral nucleic acid and proteins are synthesized using host cell machinery. The process follows the central dogma of molecular biology:

• DNA is transcribed into mRNA in the nucleus.

• mRNA is translated into proteins in the cytoplasm.

Central Dogma Equation: $ext{DNA} ightarrow ext{mRNA} ightarrow ext{Protein}$

Examples of Biosynthesis Pathways

• Positive-sense ssRNA virus: Genome acts as mRNA; translated directly into proteins (e.g., Rhinovirus).

• Negative-sense ssRNA virus: Genome must be transcribed into mRNA by viral RNA-dependent RNA polymerase (e.g., Rabies virus).

• Double-stranded RNA virus: Genome is unwound and transcribed into mRNA (e.g., Rotavirus).

Assembly, Maturation, and Release

• Lysis: Host cell bursts, releasing naked viruses.

• Budding: Enveloped viruses acquire their envelope as they exit the host cell.

• Exocytosis: Viruses are released in vesicles from the host cell.

Virus Latency

Some animal viruses can remain dormant in host cells for years (latency). If viral DNA is incorporated into host DNA, the condition is permanent (e.g., HIV, chickenpox, herpes virus).

RT-ssRNA Virus Replication Cycle

Retroviruses (e.g., HIV) copy their RNA to DNA using reverse transcriptase. The DNA is integrated into the host genome, establishing latency.

Viral Diseases: Measles and Herpes

Measles Virus (Morbillivirus)

• Etiology: Measles virus (Morbillivirus), ssRNA (-), helical capsid, enveloped.

• Virulence Factors:

  • Hemagglutinin: attaches to host epithelial cell receptors.

  • Fusion protein: causes host cells to fuse and form syncytia, allowing viral spread and evasion of antibodies.

• Clinical Features:

  • Initial symptoms: sore throat, dry cough, headache, conjunctivitis, swollen lymph nodes, fever.

  • Koplik's spots: oral lesions preceding rash.

  • Maculopapular rash: spreads from head to trunk and extremities.

• Transmission: Airborne droplets; virus enters via nose, mouth, or conjunctiva.

• Diagnosis: Clinical signs (Koplik's spots, rash).

• Treatment: No specific antiviral; ribavirin may be used; antibiotics for secondary bacterial infections.

• Prevention: Live attenuated vaccine (MMR).

• Distinguishing Features: Rash is maculopapular; secondary bacterial ear and sinus infections are common.

• Epidemiology: Highly contagious; humans are the only host; vaccination has reduced incidence; outbreaks occur in unvaccinated populations.

Herpes Simplex Virus (HHV-1 and HHV-2)

• Etiology: Human Herpes Viruses 1 and 2 (dsDNA, icosahedral capsid, enveloped).

• Virulence Factors:

  • Envelope glycoproteins: adhesion and fusion, formation of syncytia.

  • Inactivation of complement; continual shedding even without symptoms.

• Clinical Features:

  • Lesion sites: lips (herpes labialis), fingers (herpes whitlow), conjunctiva (ocular herpes), genitals (herpes genitalis).

  • Blisters (vesicles) filled with virions; painful ulcers after vesicle rupture.

  • Latent infection: virus remains dormant in nerve cells, with periodic reactivation.

• Transmission: Direct contact with infected mucous membranes or skin.

• Prevention: Use of gloves by healthcare workers; avoiding contact with lesions.

• Epidemiology: HHV-1: acquired by 80% of children worldwide by age 2; HHV-2: acquired between ages 15-29, often sexually transmitted; both can be spread between oral and genital sites; neonatal infections can be fatal.

Additional info:

• Tables and diagrams have been described in text for clarity.

• Key terms and processes have been expanded for academic completeness.