Virology: Virus Properties

• Viruses

General Properties

• Viruses are the smallest infectious agents and contain either RNA or DNA as their genome.
• The viral nucleic acid is encased in a protein shell, sometimes surrounded by a lipid-containing membrane.
• The entire infectious unit is called a virion.
• Viruses are parasites at the genetic level, replicating only in living cells.
• They are inert in the extracellular environment but contain necessary information to cause the infected host cell to synthesize virus-specific macromolecules.
• During replication, viral nucleic acid and coat proteins are produced; coat proteins assemble to form the capsid.
• The capsid encases and stabilizes the viral nucleic acid against the extracellular environment and facilitates attachment and penetration into new susceptible cells.
• Viruses are obligatory intracellular parasites.
• They are inert outside living host cells, but viral nucleic acids become active inside a host cell, leading to viral multiplication.

Distinctive Features of Viruses

• Contain a single type of nucleic acid: either DNA or RNA.
• Have a protein coat, sometimes enclosed by a lipid, protein, and carbohydrate envelope, that surrounds the nucleic acid.
• Multiply inside living cells using the host cell's synthesizing machinery.
• Cause the synthesis of specialized structures that can transfer the viral nucleic acid to other cells.

Viral Size and Shape

• Viral sizes are determined with the aid of electron microscopy.
• Viruses range in size from 20 to 1000 nm.

Virus Discovery

• Viruses were first discovered using porcelain filters that could remove all bacteria visible under a microscope.
• In 1886, Adolph Meyer demonstrated that tobacco mosaic disease could be transferred between plants via liquid plant extracts.
• In 1892, Dmitri Ivanowski showed the disease could still be transmitted after filtering out viable bacteria.
• It was later proven that these "filterable" infectious agents were a new type of very small, disease-causing particle.

Viral Morphology

• Viruses are noncellular, meaning they lack cellular structure, including organelles, ribosomes, and a plasma membrane.
• Viruses are composed of a nucleic acid genome surrounded by a protein coat called a capsid.
• The genome and capsid together are called the nucleocapsid.
• Viruses come in various shapes and sizes, which are consistent within each viral family.
• Genomes can be either RNA or DNA.
• Viral capsids are composed of individual subunits called capsomeres.
• Capsids can be simple helices, polyhedral "spheres," or complex structures.

Classification of Viruses

• Viruses are classified based on their nucleic acid type (DNA or RNA), strand type (single or double), and presence of an envelope (enveloped or unenveloped).

Viral Replication

• The viral replication cycle is also called the infectious cycle.
• It happens within a host cell.
• The stages of viral replication are adsorption/attachment, penetration/virus entry, uncoating, macromolecular synthesis, viral assembly, and release.
• Adsorption/Attachment: Virus attaches to host cell receptor.
• Penetration/Virus Entry: Virus enters host cell via direct penetration, endocytosis, or fusion with the cell membrane.
• Uncoating: The capsid is lost.
• Macromolecular Synthesis: Genome enters cytoplasm (for most RNA viruses) or nucleus (for most DNA viruses); production of nucleic acids and protein polymers.
• Viral Assembly: Structural proteins, genomes, and viral enzymes are assembled into virus particles and acquire envelopes during "budding."
• Release: Virus is released through cell lysis (lytic virus) or budding from cytoplasmic membranes.

Viruses at a Glance

• Double-stranded DNA viruses are generally naked except for Poxvirus, Herpesvirus, and Hepadnavirus, which are enveloped.
• Single-stranded RNA viruses are enveloped except for Caliciviridae, Picornaviridae, and Reoviridae, which are naked.
• Icosahedral capsids are common, with Poxvirus having a complex capsid.
• DNA viruses replicate in the nucleus, except for Poxvirus, which replicates in the cytoplasm.
• The largest DNA virus is Poxvirus and the smallest is Parvovirus.
• Hepatitis B is the only DNA hepatitis virus.
• Single-stranded RNA viruses generally have enveloped capsids, except for Caliciviridae, Picornavirus and Reovirus which are naked.
• With the exception of Orthomyxovirus and Retrovirus which have cytoplasmic and nuclear phase the RNA viruses replicate in the cytoplasm.

Outcome of Viral Replication

• Productive Infection: Provirus is translated into messenger RNA.
• Creates a new virus, a lytic cycle that infects additional cells.
• Transcription is quiet for latent infection.
• Virions are the whole infections virus that is produced during infection.
• Abortive Infection: Occurs when a virus replicates in a non-permissive host cell.
• Viral replication generates offspring that are incapable of infecting further host cells.
• Restrictive Infection: Infective viral progeny are created at times when the host cell is transiently receptive.
• Virus persists within the cell without creating infective viral progeny at other times or results in viral release but no cell death.

Mechanisms of Viral Multiplication

• Viruses can multiply by the lytic or lysogenic cycle.
• Lytic Cycle: Ends with lysis and death of the host cell.
• Lysogenic Cycle: The host cell remains alive.
• Also known as temperate or non-virulent infection, it uses the existing host cell as a temporary shelter as opposed to destroying it.
• Phage DNA is used by injected into the cell, creating a prophage.
• Prophage is copied as long as the host cell divides, but it doesn't affect any of the proteins necessary to generate offspring.
• The bacterial hosts are often unaffected by this mechanism, so the virus is passed to future generations of host cells.

Bacteriophages

• Viruses that infect bacteria.
• Replicate as obligate intracellular parasites in bacteria.
• act as powerful regulators of bacterial populations in natural ecosystems and are found in soil, plants, rivers, and the human microbiome.
• The primary steps are adsorption/attachment, penetration, biosynthesis, maturation, and lysis and release.
• Adsorption/Attachment: Bacteriophage adsorption is the beginning of the infection process, primarily located on the tail fibers to interact with the specific receptors present on bacterial cell walls.
• Penetration: Bacterial walls are weakened by the found Lysozyme tails. Tail, tubes, and comes in contact with the cell membrane. Viral DNA moves from head via the tube to the inside, the bacterial cytoplasm, as phage capsid remains outside.
• Biosynthesis: Once the DNA has reached bacterial cytoplasm the nucleic acid and protein occur. The induced protein synthesis is halted, the infected DNA degrades, and viral proteins interfere with transcription which leads to the repression of translation.
• Maturation: DNA and capsids, are the bacterial and phage components and assembled into complete virions. Both heads and tails are assembled from the gene products and protein subunits. Heads are filled with the DNA and attached to the trail.

Uses for Phages

• Can be studied as model organisms for insight. Can give a better understanding for both viral gene expression or basic genetic concepts.
• Are often used as a replacement for antibiotics.
• Can be utilized in constructing muants and to transfer genes of interest from one bacterium to another. This find wide use in recombinant DNA technology.

Examples of DNA and RNA Viruses and the Diseases They Cause

DNA Viruses

• Adenoviridae: Includes human adenoviruses, causing respiratory infections, conjunctivitis, and gastroenteritis.
• Hepadnaviridae: Includes Hepatitis B virus (HBV), causing hepatitis.
• Herpesviridae: Includes Herpes simplex virus 1 and 2, varicella-zoster virus, cytomegalovirus, Epstein-Barr virus, causing various infections such as oral and genital herpes, chickenpox, shingles, mononucleosis.
• Papillomaviridae: Includes Human papilloma viruses, causing papillomas and warts with sexually transmitted infections. Most common concern is cervical and penile cancer.
• Parvoviridae: Includes Parvovirus B-19 which causes erythema infectiosum, known as fifth disease.
• Polyomaviridae: Includes BK and JC polyomaviruses, can cause pneumonia infections.
• Poxviridae: Includes smallpox, monkeypox, and vaccinia. All of these are diseases of the skin.

RNA Viruses

• Arenaviridae: Includes Lymphocytic choriomeningitis virus, and Lassa fever virus.
• Astroviridae: Includes Gastroenteritis-causing astroviruses.
• Bunyaviridae: Arboviruses such as the California encephalitis and Lacrosse viruses; or hantaviruses such as sin nombre and similar strains.
• Caliciviridae: Inlcudes Noroviruses and hepatitis E virus.
• Coronaviridae: Includes Coronaviruses such as SARS coronavirus.
• Filoviridae: Includes Ebola and Marburg hemorrhagic fever viruses.
• Flaviviridae: Includes Yellow fever, dengue, West Nile, Japanese encephalitis, and St. Louis encephalitis, nonarboviruses including hepatitis C virus.
• Orthomyxoviridae: Includes Influenza A, B, and C viruses.
• Paramyxoviridae: Includes Parainfluenza viruses, mumps virus, measles virus, respiratory syncytial virus, metapneumovirus, Nipah virus.
• Picornaviridae: Includes Polio, cosackie A and B, echo, and the Enteroviruses which causes Hepatitis A virus, rhinoviruses.
• Reoviridae: Rotavirus and the Colorado tick fever virus.
• Retroviridae: Human Immunodefieciency and T-lymphotropic viruses.
• Rhabdoviridae: Rabies virus.
• Togaviridae: Arboviruses such as Eastern, Western, and Venezuela equine encephalitis viruses and rubella virus.

Baltimore Classification

• Group I: Viruses contain double-stranded DNA (dsDNA) as their genome produce mRNA through transcription using host cell enzymes.
• Group II: Viruses have single-stranded DNA (ssDNA) and convert to dsDNA to transcribe mRNA.
• Group III: Viruses use dsRNA and separate the strands to create a template for mRNA production using the viruses RNA polymerase.
• Group IV: Viruses contain ssRNA with a positive polarity which means RNA can directly serve as mRNA.
• Group V: Viruses contain ssRNA with a negative polarity, meaning sequence will be complementary to mRNA,
• Group VI: Viruses have diploid (copies) is converted to dsDNA to produce mRNA using the reverse transcriptor enzyme.
• Group VII: Viruses have partial dsDNA, creating ssRNA intermediates which act as mRNA. Also convert back to dsDNA with the revse transcriptor enzyme for genome replication.