Introduction to Viruses

Introduction to Viruses

• Viruses are the smallest infectious agents, ranging from 20 to 300 nm in diameter.
• They contain only one type of nucleic acid: either RNA or DNA, as their genome.
• The nucleic acid is enclosed in a protein shell.
• It may be surrounded by a lipid-containing membrane.
• The entire infectious unit is called a virion.
• Viruses are inert outside living cells.
• They can only replicate within living cells, acting as parasites at the genetic level.
• Viruses are classified into four groups based on their hosts: animal, plant, insect, and bacteriophages.

General Biological Characteristics of Viruses

• Viruses are minute, obligate intracellular parasites that replicate in susceptible living cells.
• An adult virus (virion) consists of a central core of nucleic acid (DNA or RNA, but not both) which is genetic material and a protein shell called a capsid that coats the viral genome.
• Viruses lack organelles like ribosomes and the necessary apparatus for protein transfer.
• They also lack particular enzymes for metabolism, mitochondria, and other components needed for independent living.
• Viruses multiply through replication depending on their nucleic acids, and not by binary fission.
• Viruses are biologically inactive when dormant.
• Common antibiotics and factors that affect metabolism do not affect them.
• Some antibiotics, like actinomycin and rifampicin, can hinder the biological synthesis of cells and hamper the replication cycle.
• Most viruses are sensitive to interferon, and infected cells can produce interferon, protecting other cells from viruses.
• Some viruses cause latent infections by fusing their nucleic acids with the host cell's DNA, leading to multiplication with each division until the environment is suitable for separation.
• An electronic microscope, discovered in 1940, can distinguish viruses.
• Viruses are metabolically inactive outside their hosts.
• Some viruses have an envelope made of lipoprotein outside the nucleocapsid or nucleoprotein (nucleic acid + capsid).

Symmetry of Viruses

• Symmetry refers to the shape of the capsid or nucleocapsid arranged with capsomers.
• Protomers aggregate to form capsomeres.
• Nucleic acid controls the aggregation between the capsid and the nucleic acid and inherits the morphological structure of the virus.
• Types of viral capsid symmetry include helical symmetry (enveloped or naked), cubical symmetry (enveloped/naked), complex symmetry, and binal symmetry (cubical with helical).
• Helical symmetry is found in RNA viruses where capsomers and nucleic acid are coiled like a helix or spiral, whether straight/non-straight, enveloped/naked.
• Cubical symmetry viruses appear spherical under electron microscopy, shown as hexagonal (6 angles) cubic or icosahedron (cubical with 20 faces), with each vertex representing the attachment of 5 triangles.
• Complex symmetry pertains to viruses that do not take cubical and helical shapes (e.g., Pox viruses), appearing like bricks.
• Binal symmetry is seen in Bacteriophages (e.g., Coliphage), where the phage's head has a polygonal cubical shape and a cylindrical tail with helical symmetry.

Classification and Nomenclature of Viruses

• Virus classification organizes viruses into a systematic arrangement.
• Taxonomic systems for all viruses were established in 1973 by the International Committee for the Taxonomy of Viruses (ICTV).
• The ICTV provides useful virus classification and nomenclature via its discussions and reports on virus taxonomy.
• According to ICTV, there are 9 orders, 131 families, 46 subfamilies, 803 genera, and 4853 virus species affecting humans, animals, and plants.
• The highest taxonomic group is the order, with names ending in "-virales".
• Families are named with the suffix "-viridae" (e.g., Paramyxoviridae).
• Subfamilies have the suffix "-virinae" (e.g., Paramyxovirinae).
• Genera are named with the suffix "-virus" (e.g., Ebolavirus).
• Species are identified through antigenic differences and nucleic acid sequence studies.
• Delineation of order is based on common properties between several families.
• Outlining of families relies on common properties among several genera.
• In formal taxonomic usage, the first letters of virus family, subfamily, and genus names are capitalized and italicized, while species names are not capitalized unless derived from a place name.
• Family delineation consideres: biochemical composition, replication strategy, genome organization, virion morphology, physical properties, genome properties, protein/lipid/carbohydrate properties, and antigenic/biological properties.

Virus Classification

• Virus morphology is a factor, including size/shape/symmetry/envelope presence.
• Virus genome properties considered: type of nucleic acid (DNA/RNA, single/double-stranded, linear/circular, segmented/non-segmented) and polarity.
• (+) sense RNA viruses code directly for protein, while (-) sense RNA viruses do not.
• Physiochemical properties evaluated: molecular mass, pH stability, thermal stability, and susceptibility to chemical/physical agents like ether and detergents.
• Virus protein traits assessed: number, size, functional activities of structural/nonstructural proteins, amino acid sequence, modifications, and presence of specific enzymes.
• Antigenic properties induce the host immune response.
• Biological properties: encompass natural host range, transmission mode, vector relationships, pathogenicity, tissue tropisms, pathology, and symptomatology.

Pathogenesis of Viral Infection

• Pathogenesis is the process by which a virus produces disease in the host.
• Pathogenicity is the ability of viruses to produce disease by entering susceptible hosts, multiplying, and causing harmful/lethal effects.
• Virulence is the degree of aggressiveness of viruses.
• Many viruses are non-pathogenic or poorly pathogenic due to their inability to produce disease.

Virulence factors

• For a virus to produce disease, it must enter the host by overcoming natural barriers, multiply in host cells, interfere with the host's defense mechanisms, damage tissues, and have a genetic basis.

Entry of Viruses into the Host

• Viruses enter hosts through respiratory/oral routes, skin (cutaneous), conjunctiva, urinary/genital tracts, arthropod bites, or the placenta.
• Intact skin is a strong barrier, so viruses enter through breaks like cuts and punctures, or via insect/animal bites.
• The respiratory tract is important for defense, but viruses like influenza can adhere strongly to cilia, and some microorganisms can promote viral growth.
• The digestive system, a common entry route, possesses defense mechanisms like mucociliary action, macrophages, high acidity, proteolytic enzymes, bile, and local immunoglobulin IgA.
• Interaction issues cause viruses to struggle to establish themselves in the urogenital tract, though some, like herpes, overcome the local defenses.
• Conjunctiva is protected by secretions/wiping, but trauma incidents make viral infection possible.

Spread of Viruses within the Host

• After entry, viruses spread to different parts of the body through the lymph/blood system, breaching tissue junctions, moving through mucous/lumen contents, and nerves.
• The ability to overcome humoral (B-cells) and cellular (T-cells) defense mechanisms determines tissue spread.
• The size of virus particles influences the efficacy of ingestion by macrophages.
• Once viruses reach the bloodstream via the lymphatics, they can localize anywhere.
• Viraemia defines the presence of viruses in the blood, resulting from viruses entering from infected tissues.
• Peripheral nerves play a role in certain virus spreads, and pregnancy may lead to mother-to-fetus transmission through the placenta.

Viral Receptors and Relationship to Infectivity

• Initial interaction between determinants on the virus and receptor binding sites on the host cell determines viral infection.
• The presence or absence of specific cell surface receptors influences the tissue tropism of viruses.

Multiplication of Viruses

• Viruses multiply in target sites after entry through attachment, penetration, uncoating, macromolecular synthesis, maturation, assembly, and release.
• Replication factors, including host cell factors, support the multiplication of viruses.
• N-acetyl neuraminic acid residues of glycoprotein are examples of cell surface receptors for paramyxoviruses.

Interference with Host Defense Mechanism

• Viruses overcome non-specific and immune-specific defense mechanisms to multiply, localize, and produce disease. Non-specific defense mechanisms include:
  • Humoral factors: Complement components, lipids, and non-lipid inhibitors, found in serum, urine, milk, and intestinal mucosa, destroy viruses.
  • Cellular factors: Phagocytes, natural killer cells eliminate many viral infections.
  • Environmental factors: PH, temperature and micronutrients.

Replication of Viruses (Viral Multiplication)

• Viruses rely on host cell machinery as intracellular parasites.
• Knowledge of viral replication is important for understanding pathogenesis, immunity, and chemotherapy.
• Viral replication steps: attachment (adsorption), penetration, uncoating and release, transcription, translation, nucleic acid replication, assembly, and virion release summarized into 5 steps:
  • Cell infection: attachment, penetration, and uncoating.
  • mRNA production: nucleic acid transcription for mRNA.
  • Viral protein synthesis: mRNA translation.
  • Genome replication: production of new viral nucleic acids.
  • Virus assembly/release: encapsidation and release. The routes of cell infection: depend on cell types (animal, bacteria, and plants).

Steps of Cell Infection

• Attachment (adsorption): requires specific receptors on host cells, electrostatic attraction (enhanced by Ca and Mg ions), and Brownian movement (influenced by temperature).
• Penetration: may occur through endocytosis, fusion, and translocation, in which the virus must penetrate the membrane, with naked viruses using pinocytosis or viropexis.
• Uncoating: The eclipse period occurs, with no infectious particles demonstrable.
• The time required ranges from 4-12 hours for DNA viruses and 2-10 hours for RNA viruses.

mRNA Production (Transcription)

• Viral genome must be transcribed into mRNA.
• RNA becomes mRNA in some RNA viruses.
• dsDNA viruses undergo transcription (except poxviruses) in the infected cell's nucleus using cellular DNA-dependent RNA polymerase II, whereas transcription in poxviruses occurs in the cytoplasm.
• Transcription in RNA viruses is more complex because mRNA requires transcriptase activity.
• Retroviruses must reverse-transcribe their nucleic acid virion-associated prior to transcription.

Viral Protein Synthesis (Translation)

• Viral mRNA attaches to ribosomes, is translated as a virus-specific protein.
• Translation's produced components become enzymes to synthesize viral nucleic acids and part of the capsid structure, which tRNA transports to essential locations.

Replication of Viral Nucleic Acid

• Double helical DNA strands separate, and each synthesizes a complementary strand.
• Bases join: Binding of Adenine to Thymine, and Guanine to Cytosine.
• RNA viruses use a specific polymerase enzyme.

Assembly and Release

• Assembly varies for proteins and genomes - DNA viruses assemble in the nucleus (except poxviruses), and RNA viruses assemble in the cytoplasm.
• This period varies (6-8) hours or longer in some viruses like orthomyxo and paramyxo.
• Release varies: release to surroundings, via cytoplasm paths, liberation from membranes, and budding from membranes.
• The release of mature virions from the infected cell is mediated by lysis and budding.