Viruses: Structure, Replication, and Viral Diseases (Measles, Herpes)

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 and are classified alongside viroids and prions, which are also non-cellular infectious entities.

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

• Virus: Tiny acellular agent containing either DNA or RNA as its genome, but lacking cellular structure.

• Prion: Infectious protein particle lacking nucleic acids, replicates by converting normal proteins into abnormal forms (e.g., prion diseases).

• Viroid: Naked RNA molecule that infects plants, lacking a protein coat.

Are Viruses Alive?

Viruses are not considered living organisms because they do not carry out essential life processes independently.

• Not made of cells (acellular)

• Cannot reproduce independently

• Do not grow or undergo division

• Do not perform metabolism or transform energy

• Cannot synthesize proteins on their own

Structural Characteristics of Viruses

Basic Components

Viruses are composed of nucleic acids (DNA or RNA), proteins, and sometimes a lipid envelope derived from the host cell.

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

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

• Envelope: Lipid membrane acquired from the host cell, containing viral glycoproteins and spikes for host recognition.

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

Formula: $\text{Nucleic acid} + \text{Capsid} = \text{Nucleocapsid}$

Virus Envelope

The envelope is derived from the host cell membrane during viral replication or release. It consists of phospholipids and viral glycoproteins, which play a crucial role in host cell recognition and penetration.

• Envelope proteins and glycoproteins are essential for viral infectivity.

• Spikes on the envelope facilitate attachment to host cells.

Virus 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 surrounded by an envelope (e.g., Herpesvirus).

Virus Sizes

Viruses are much smaller than cells and organelles. For example:

• Poliovirus: ~30 nm

• Bacteriophage T4: ~225 nm

• Smallpox virus: ~200 nm x 300 nm

• Red blood cell: ~10,000 nm diameter

Families of Viruses That Affect Humans

Classification by Genome Type

Viruses are classified based on their nucleic acid type and structure. Major families and examples are summarized below:

Genome Type	Viral Family	Important Genera
Single-stranded DNA	Parvoviridae	Parvovirus
Double-stranded DNA	Herpesviridae	Herpes simplex virus
Single-stranded RNA (+)	Picornaviridae	Poliovirus
Single-stranded RNA (-)	Orthomyxoviridae	Influenza virus
Double-stranded RNA	Reoviridae	Rotavirus
Retrovirus (ssRNA-RT)	Retroviridae	HIV

Bacteriophage and Animal Viral Structure Compared

Host Specificity

Viruses are highly specific to their host organisms:

• Plant viruses infect plant cells

• Bacteriophages infect bacterial cells

• Animal viruses infect animal cells

Animal Virus Replication

General Replication Cycle

Animal viruses replicate through a series of steps:

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

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 proteins (spikes, glycoproteins) and host cell receptors.

• Determines host range and tissue tropism.

Penetration

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

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

• Endocytosis: Host cell engulfs the virus, which is then uncoated to release the genome.

Biosynthesis

Viral nucleic acid and proteins are synthesized using host cell machinery. The central dogma applies:

• DNA is transcribed to mRNA in the nucleus.

• mRNA is translated to protein in the cytoplasm.

Formula: $\text{DNA} \rightarrow \text{mRNA} \rightarrow \text{Protein}$

Assembly, Maturation, and Release

• Lysis: Host cell bursts, releasing naked viruses.

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

• Exocytosis: Viruses are released via vesicles.

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).

RT-ssRNA Virus Replication Cycle

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

• HIV is a ssRNA (+) virus with capsid and envelope.

• Replication involves reverse transcription and integration into host DNA.

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: Fuses host cells, forming syncytia (giant cells with multiple nuclei).

Clinical Features

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

• Characteristic oral lesions: Koplik's spots.

• Rash: maculopapular, spreads from head to trunk and extremities.

Transmission

• Spread via respiratory droplets (airborne).

• Humans are the only host.

Diagnosis and Treatment

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

• Treatment: No specific antiviral; Ribavirin (guanosine analogue) may inhibit viral polymerases; antibiotics for secondary bacterial infections.

Prevention

• Live attenuated vaccine (MMR).

Distinguishing Features

• Maculopapular rash

• Secondary bacterial ear and sinus infections are common

Epidemiology

• Highly contagious

• Vaccination has reduced spread

• Eradicated in USA in early 2000s, but cases have re-emerged due to unvaccinated individuals

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

Etiology

• Human Herpes Viruses 1 and 2 (HHV-1, HHV-2)

• dsDNA

• Icosahedral capsid

• Enveloped

Virulence Factors

• Envelope glycoproteins for adhesion and fusion

• Formation of syncytia

• Inactivation of complement

• Latent infection with continual shedding

Clinical Features

• Lips: herpes labialis (cold sores)

• Fingers: herpes whitlow

• Conjunctiva: ocular herpes

• Genitals: herpes genitalis

Pathogenesis

• Initial infection: replication in epithelial cells, inflammation, cell death, vesicle formation

• Latent infection: virus remains dormant in nerve cells, reactivates intermittently

Diagnosis and Prevention

• Diagnosis: characteristic lesions

• Prevention: gloves for healthcare workers

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 mucous membranes

• Herpes infections in adults are not life-threatening, but neonatal infections can be fatal

Summary Table: Virus Families Affecting Humans

Genome Type	Viral Family	Important Genera
Single-stranded DNA	Parvoviridae	Parvovirus
Double-stranded DNA	Herpesviridae	Herpes simplex virus
Single-stranded RNA (+)	Picornaviridae	Poliovirus
Single-stranded RNA (-)	Orthomyxoviridae	Influenza virus
Double-stranded RNA	Reoviridae	Rotavirus
Retrovirus (ssRNA-RT)	Retroviridae	HIV

Additional info: The notes cover topics from Chapter 13 (Characterizing and Classifying Viruses, Viroids, and Prions) and Chapter 14 (Infection, Infectious Diseases, and Epidemiology), as well as relevant structural and replication details from Chapter 3 and Chapter 8.