History of Virology & Virus Discovery

• Viruses and virions are discussed with Dr. Tedjar; the question is posed, "Why should we be interested in viruses?".

History of Virus Discovery

• Adolf Mayer (1843-1942) described a disease of tobacco plants called tobacco mosaic and determined it was infectious.
• The first experiment involving an ultra-filterable agent smaller than bacteria was the transmission of tobacco mosaic by Dimitri Ivanovski (1864-1920) from plant filtrates in 1892.
• Ivanovski initially maintained a bacterial explanation of viruses in the form of spores.
• Martinus Beijerinck (1851-1931) understood the observation's consequences six years later by repeating it, coining the term "contagium vivum fluidum".

Modern Advancements in Virology

• Kary Mullis developed the polymerase chain reaction (PCR) in 1985, which is used in COVID-19 diagnosis.
• PCR allows specific amplification of tiny amounts of nucleic acids and has revolutionized viral diagnostics.
• New viruses are still being discovered, such as the hepatitis C virus in 1989, Nipah virus in 1999, Metapneumovirus in 2001, and SARS virus in 2003.
• Harald zur Hauzen was awarded in 2008 for his work on cervical cancer due to papillomavirus.
• Middle East Respiratory Syndrome (MERS) was identified in 2012.
• Coronavirus/19 emerged in 2019.

Definition of a Virus

• The term "virus" comes from Latin, meaning "poison".
• A virus is a biological entity that requires a host cell to multiply, using the host's components.
• Viruses are microscopic infectious agents with only one type of nucleic acid (DNA or RNA).
• They reproduce inside a cell and parasitize both multicellular organisms (200 species are pathogenic to humans) and unicellular organisms like bacteriophages.
• Virology is the science that studies viruses.

Characteristics of Viruses

• Viruses resemble living organisms as they consist of characteristic molecules and possess genetic material for reproduction and evolution.
• They are considered acaryotic due to the absence of cellular structure, metabolism, and growth.
• Viruses develop only by parasitizing living cells, making them obligate intracellular parasites.
• Viruses usually range in size from 10 to 400 nm in diameter.

Basic Viral Particle Shapes

• Icosahedral, naked; as seen in the poliomyelitis and hepatitis A viruses (both Picornaviridae) and Adenoviridae.
• Helical, naked; as seen in the tobacco mosaic virus, common in plant viruses but not found in human viruses.
• Icosahedral, enveloped; as seen in Herpesviridae, yellow fever virus (Flaviviridae), and rubella virus (Rubivirus).
• Helical, enveloped; as seen in rabies virus (Rhabdoviridae), influenza virus (Orthomyxoviridae), measles, and mumps viruses (both Paramyxoviridae).

Virion

• The virion, or viral particle, represents the structural unit of a virus.
• The virion can be defined as the final product of viral development, corresponding to a mature, infectious, and extracellular viral particle.
• It consists of two constant structural elements: the viral genome and the capsid.

Helical Capsids

• Helical capsids resemble hollow tubes made of proteins.
• Influenza virus RNA is included in fine and flexible helical capsids, folded into an envelope.

Icosahedral Capsids

• Icosahedral capsids are regular polyhedra with 20 equilateral triangular faces and 12 vertices.
• Capsomeres are ring-shaped units composed of 5 or 6 protomers.
  • Pentamers (pentons) have 5 subunits.
  • Hexamers (hexons) have 6 subunits.

Complex Capsids

• Viruses with binary symmetry have an icosahedral symmetry (head) and a helical symmetry (tail).

Virus Variation

• A large variety of viruses cause severe, contagious diseases, known as viroses in plants.
• Common examples of viral diseases in animals and humans include the common cold, influenza, chickenpox, measles, and infectious mononucleosis.
• More severe diseases, such as AIDS, avian influenza, and smallpox, are also caused by viruses; The Ebola virus causes hemorrhagic fevers.
• Coronavirus/19 in 2019 and its 2021 variants are also a part of virus variations.
• The capacity of a virus to cause disease is described in terms of virulence.

Viral Nucleic Acid

• Each viral particle contains only one type of nucleic acid, either DNA or RNA.
• Viruses are separated based on their DNA or RNA composition.
• Retroviruses, which are RNA viruses, are reverse transcribed into DNA in the host cell.
• Viral replication involves the introduction of the viral genome into a cell, which then produces new viruses through biosynthesis, also referred to as replication.

DNA Viruses

• A DNA virus possesses DNA in its genome and does not use an RNA intermediate during its replication.
• ADN-dependent DNA polymerase is used to replicate DNA viruses.
• The DNA can be single-stranded (ssDNA) or double-stranded (dsDNA), with the latter being more common.

Virus Classification

• Viruses are classified based on the host, nucleic acid type (DNA or RNA), symmetry type (cubic, helical, or combined), and the existence of an envelope (naked or enveloped).
• These three criteria define the virus family.
• There is also an unofficial classification used by clinicians, based on the host, transmission mode, entry route, and pathological effects (e.g., enteric, respiratory, or oncogenic viruses).

Baltimore Classification

• The Baltimore classification system categorizes viruses based on their genome and replication strategy.
  • Class I: Double-stranded DNA viruses.
  • Class II: Single-stranded DNA viruses.
  • Class III: Double-stranded RNA viruses.
  • Class IV: Positive-sense single-stranded RNA viruses.
  • Class V: Negative-sense single-stranded RNA viruses.
  • Class VI: Single-stranded RNA viruses that replicate through a DNA intermediate.
  • Class VII: Double-stranded DNA viruses that replicate through an RNA intermediate.
• Class IV viruses have a genome that codes directly for viral proteins, like an mRNA messenger.
• Class V viruses possess genomes do not code directly for proteins.
• Classes VI and VII require reverse transcription (molecule of RNA copied into DNA) during viral replication.
• Whether or not polymerase is present in the viral particle varies depending on the class.

RNA Viruses: Group IV and V

• Group IV viruses are positive-sense single-stranded RNA viruses (or mRNA-type viruses).
• Positive-sense RNA polarity allows host ribosomes to directly decode and immediately synthesize proteins; This group replicates in the cytoplasm and can be divided into two groups.
  • Viruses with polycistronic mRNA use genomic RNA to form mRNA, translated into polyproteins that are cleaved to form mature proteins.
  • Viruses with complex transcription require a subgenomic mRNA, ribosomes, and a proteolytic treatment of polyproteins where different mechanisms produce proteins from the same RNA strand.
• Family examples: Astroviridae, Caliciviridae, Coronaviridae, Flaviviridae, Picornaviridae, Arteriviridae, and Togaviridae.
• Group V viruses are negative-sense single-stranded RNA viruses.
• RNA viruses with negative polarity and all genes defined as antisense cannot be directly decoded by host polymerases to produce proteins immediately; Instead, viral polymerases transcribe them into a "readable" positive-polarity form, and are divided into two groups.
• Family examples: Arenaviridae, Orthomyxoviridae, Paramyxoviridae, Bunyaviridae, Filoviridae, and Rhabdoviridae (includes the rabies virus).

Viral Taxonomy and Specificity

• There are fundamental differences between viruses and cellular organisms, explaining the specificity of viral nomenclature.
• Names used for virus determination include:
  • Orders (suffix -virales, e.g., Mononegavirales).
  • Families (-viridae, e.g., Luteoviridae).
  • Subfamilies (-virinae, e.g., Paramyxovirinae).
  • Genera (-virus, e.g., Retrovirus).
• Viral species names are represented by examples such as Tobacco mosaic virus.

Picornaviridae Family

• Rhinovirus primarily affects the respiratory system.
• Enterovirus affects the digestive and nervous systems.
• Cardiovirus affects the heart, nervous system, and other systems.
• Hepatovirus affects the liver.

What Defines a Virus (André Lwoff, 1953)

• André Lwoff defined three fundamental characteristics of viruses in 1953.
  • Viruses contain only one type of nucleic acid (DNA or RNA), which constitutes the viral genome.
  • Viruses reproduce from their genetic material through replication.
  • Viruses exhibit absolute intracellular parasitism.

Viral Genome, Envelope and Capsid Structure

• The presence of certain elements helps differentiate different virus types.
  • The nature of genetic material: DNA or RNA.
  • The structure of the nucleic acid: Monocatenary or bicatenary.
  • The form of the nucleic acid: Linear, circular, non-segmented, or segmented.
• Viruses can be naked or enveloped.
• Symmetry includes helical, icosahedral, or unknown symmetries.

Virus Structure

• Viral structure includes the nucleic acid (genome) and the capsid (protein coat).
• Viruses can be categorized as having an RNA, or DNA double-strand(bicatenary) or single strand (monocatenary).
  • The capsid is a rigid protein shell that encloses and protects the nucleic acid, and nucleic acid + capsid = nucleocapsid.
• Naked viruses consist of only the nucleocapsid, while enveloped viruses have a lipid envelope surrounding the capsid.
• The lipid envelope is a lipid bilayer with embedded proteins or glycoproteins.
• Examples of enveloped viruses include the Influenza and HIV.

Viral Genome and Proteins of Capsid

• The viral genome is typically composed of one or more strands of deoxyribonucleic or ribonucleic acid, in linear or circular form.
• A distinction is made between viruses that have RNA, and DNA both of which can be single or double strands, and ARN of (+) or (-) polarity.
• Capsid proteins are capable of polymerizing by self-assembly to form the viral capsid structures.
• Some viruses have matrix proteins that facilitate the connection between the nucleocapsid and the envelope, a location referred to as transmemebrane (anchorage).

Viral Envelopes

• Plant viruses are mostly naked; animal and insect viruses have an enveloped capsidial structure.
• Bacteriophages can be naked, enveloped, or have a membrane inside the capsid, enveloping the genome.
• The envelope plays a key role in virus attachment to the target cell, through interactions with glycoprotines that are specific for cell receptors.

Envelope Function

• Envelopes cause viruses to be fragile:
  • Intact structure needed to be infectious
  • Easily degraded within intestines and outer environment.
• Naked viruses are without envelopes:
  • Only a genome and capsid.
  • Survive longer than enveloped and are icosahedral.
• Epidemiology is related to the spread and transmission between subjects.
• Environments outside are not ideal for enveloped survival due to:
  • Temperature.
  • Dehydration.

Viroids

• Until 1967, the smallest plant and animal infectious agents were believed to be viruses.
• A new intracellular pathogenic agent category known as viroids was discovered, these are self-reproducing and not protected by a protein capsid..
• These cause around 15 plant diseases, using mechanical transmission (grafting, contact and wounds).
• Without a specific protein, their ability to be pathogenic is under question.

Dispersion of infection in an organism

• Once infection occurs, pathogens will disperse in these ways:
  • Virémie- transport via blood.
  • Axonal- Axon transport used.
• Dispersal also follows secondary and primary routes.
  • Site of replication primary: At the point of entry.
  • Ingestion: Consumption orally of virus.
  • Site of replication secondary: Further spreading into new tissue/organs.

Cycle of Infection by a Virus

• Cycle described in three stages.
  • Attachment: Viral genes introduce the genome.
  • Expression of genes and the replication: Protein synthesis encoded by the genome.
  • Assembly: Release and production of viral particles (Spreading).

SARS-CoV-2 Cycle

• Spike proteins latch to cell receptors that transport virus in its genomic data.
• Viral RNA translated into a form of protein.
• Synthesizing the viral genome (Copies).
• Components assemble into Virions.
  • Escape the cell to contaminate others.

Is a Virus Living or Dead?

• Varies on what definition is used.
  • Considered alive because of genome.
    • Nucleus acid passed through generations.
  • Metabolism is absence though.
    • Cells can not make proteins on their own.
    • These differences differentiate organism types.
• It's not typical jargon to describe a virus in living form, or 'kill' a virus.

Key Traits to Differentiate Virus v Bacteria

• Viruses contrast with Bacteria on many traits:
  • Growth: Aritfical mediums.
  • Fission: Cell division.
  • Particule Infectieuse: Presence of ADN/ARN
  • Ribosomes: Presence in organic material.
  • Paroi Formée: Peridoglycane.
  • Sensible: Sensitivity to antibiotics.
• Arenaviridae have ribosomes by accident, not protein based.

Viral Mutation and its Implications for SARS-CoV-2

• Viruses are required to reproduce.
• Reproduction requires information to be written as a precise copy.
  • Often times its not and errors subsist.
    • Includes: Insertions, substitutions and deletions.
• Adaptations in favor of environment occurs.

COVID-19 Variance Reason

• A variant is a new version related to its original state.
• Three variants are:
  • Africa/Sud-Africa- 2020 Signaled.
  • Japan/ Brazil-January 2021.

Omicron Variant

• First discovered November 24 by Krips in Africa, the B.1.1.529 strain.
• High Mutations- Up to 30 (2 in delta).
• November 26- Identified, is present in most countries.
  • Delta is vaccinated, easier to contract and carries a higher virulence.

How is Omicron Immune to the Vaccine?

• Inquiries suggest questions revolving if Omincron is resistatnt to vaccine C-19 27/11/2021.
• Large number of mutations cause harm.
• Spicule protein allows SARS-CoV-2 to go inside and is different than vaccine strains.

Conclusion

• An understanding of how and why the coronavirus mutates is critical to new treatments.