Viruses: Structure, Physiology, and Unique Infectious Agents ~ Chp 13

Viruses

I. General Characteristics & General Morphology

Viruses are unique infectious agents that differ significantly from cellular life forms. They are obligate intracellular parasites, meaning they require a host cell to reproduce and carry out metabolic processes.

• Not cells: Viruses lack a cell membrane and cellular organelles. They are composed of a nucleic acid core (DNA or RNA) surrounded by a protein coat (capsid). Some viruses also have an envelope derived from the host cell membrane, containing embedded viral proteins (spike proteins).

• No ribosomes: Viruses do not have ribosomes and cannot synthesize proteins independently. They rely entirely on the host cell's machinery for protein synthesis and energy production.

• Genetic material: Each mature virus particle (virion) contains only one type of nucleic acid (either DNA or RNA, never both). The nucleic acid is referred to as the viral chromosome.

• Do not divide: Viruses do not reproduce by cell division. Instead, they assemble from newly synthesized components within the host cell.

II. General Physiology

Viruses hijack the host cell's metabolic machinery to synthesize viral proteins and replicate their genetic material. The process of viral replication involves several key steps:

1. Replication enzymes and substrates: DNA or RNA nucleotides are used to replicate the viral genome.

2. Transcription enzymes and substrates: Enzymes and nucleotides required for transcription of viral genes.

3. Translation apparatus and substrates: Host ribosomes, tRNAs, and amino acids are used to translate viral mRNA into proteins.

4. Metabolic energy: ATP is required for various biosynthetic processes.

Unlike cells, viruses synthesize their components (chromosome and capsid proteins) independently and then assemble them into new virions. This is distinct from cellular reproduction, which involves cell growth and division.

III. Steps in the Viral Life Cycle

The viral life cycle consists of several distinct stages:

1. Entry: Viruses enter host cells by various mechanisms, including injection of the viral genome (bacteriophages), fusion of the viral envelope with the cell membrane (enveloped animal viruses), or endocytosis.

2. Uncoating: The viral capsid is removed, releasing the viral genome into the host cell.

3. Synthesis: Viral proteins and nucleic acids are synthesized using the host cell's machinery. The order of synthesis depends on the type of viral genome.

4. Assembly (Maturation): Newly synthesized viral genomes and capsid proteins are assembled into new virions. This process often occurs spontaneously when sufficient concentrations of components are present.

5. Release: New virions are released from the host cell, often by cell lysis (non-enveloped viruses) or budding (enveloped viruses).

IV. Synthesis in More Detail for Selected Viruses

The mechanisms of genome replication and protein synthesis differ between DNA and RNA viruses.

1. dsDNA Viruses

• The viral chromosome is a double-stranded DNA molecule.

• Host RNA polymerase transcribes viral genes into mRNA.

• Host ribosomes translate mRNA into viral proteins.

• Viral DNA is replicated using host or viral DNA polymerase.

• Late transcription and translation produce capsid proteins.

2. +RNA Viruses

• The viral genome is single-stranded RNA that functions directly as mRNA.

• Host ribosomes translate the +RNA into viral proteins.

• An important early protein is RNA-dependent RNA polymerase, which synthesizes a complementary -RNA strand from the +RNA genome.

• The -RNA serves as a template for the synthesis of additional +RNA genomes.

• With more +RNA, ribosomes can translate late genes, and the +RNA can assemble with capsid proteins.

Note: Host RNA polymerase cannot replicate RNA from an RNA template; this function is performed by the viral RNA-dependent RNA polymerase.

3. -RNA Viruses

• The viral genome is single-stranded RNA of negative polarity (not directly translatable).

• Viral RNA-dependent RNA polymerase (carried within the virion) synthesizes +RNA (mRNA) from the -RNA genome.

• +RNA is translated by host ribosomes; -RNA is transcribed by the viral RNA-dependent RNA polymerase.

4. Retroviruses

• Retroviruses have a +RNA genome but do not use it directly as mRNA. Instead, they use a unique enzyme called reverse transcriptase to synthesize a complementary DNA (cDNA) copy from the RNA genome.

• The cDNA is integrated into the host genome by another viral enzyme, integrase.

• Host RNA polymerase transcribes the integrated viral DNA into +RNA, which serves as both the genome for new virions and as mRNA for protein synthesis.

• Viral proteins are often synthesized as a single large polyprotein, which is cleaved into functional proteins by the viral protease.

Reverse transcriptase has three main activities:

• Synthesizes a complementary DNA (cDNA) from an RNA template.

• Synthesizes a complementary DNA strand from a DNA template (DNA-dependent DNA polymerase activity).

• Degrades the original RNA template (RNase H activity).

V. Viruses and Cancer

Some viruses are oncogenic, meaning they can cause cancer. This is particularly true for certain DNA viruses (e.g., human papillomavirus, HPV) and some retroviruses. Oncogenic viruses may carry genes (viral oncogenes, vONC) that disrupt normal cell cycle regulation, leading to uncontrolled cell division and tumor formation.

• Cellular oncogenes (cONC): Normal genes involved in cell growth and division. When mutated or dysregulated, they can contribute to cancer.

• Viral oncogenes (vONC): Viral genes that can transform host cells and promote cancer.

Example: HPV is a DNA virus associated with cervical cancer. Some retroviruses can also cause cancer by integrating oncogenes into the host genome.

VI. Prions

Prions are infectious protein particles that lack nucleic acids. They cause a group of neurodegenerative diseases known as transmissible spongiform encephalopathies (TSEs), which are progressive, fatal, and affect the brain and nervous system.

• Prion diseases are caused by misfolded forms of a normal host glycoprotein.

• Examples include:

  • Creutzfeldt-Jakob disease (CJD) in humans

  • Bovine Spongiform Encephalopathy (BSE, "mad cow disease") in cattle

  • Scrapie in sheep

• Transmission can occur between species, as seen with BSE and variant CJD.

VII. Viroids

Viroids are small, circular RNA molecules (300–400 nucleotides) that infect plants. They lack a protein coat and do not encode proteins. Viroids can cause significant agricultural damage by interfering with normal plant gene expression.

• Viroids are transmitted by insects or contaminated tools.

• They cause diseases in various plants, leading to economic losses.

VIII. Coat Protein Mediated Resistance

Coat protein mediated resistance is a biotechnological strategy used to protect plants from viral infections. By engineering plants to express viral coat proteins, the assembly of infecting viruses can be disrupted, preventing the completion of the viral life cycle.

• High concentrations of coat protein in the plant cell can prevent uncoating of the virus, stopping infection.

• This method has been used to protect crops and animals (e.g., chickens engineered to express the coat protein of Avian leukosis virus).

Additional info: This approach reduces the need for chemical insecticides and can help control the spread of plant viruses by insect vectors.

Summary Table: Key Features of Viruses, Prions, and Viroids

Agent	Genetic Material	Protein Coat	Replication	Host Range	Example Diseases
Virus	DNA or RNA	Yes (capsid; sometimes envelope)	Requires host cell	All life forms	Influenza, HIV, HPV
Prion	None	No	Converts normal proteins	Animals, humans	BSE, CJD, Scrapie
Viroid	RNA (small, circular)	No	Requires host cell	Plants	Potato spindle tuber disease