Introduction to Viruses

Viruses

• Viruses are acellular particles capable of infecting host cells and causing disease
• They are not free-living and require a host cell to multiply, acting as obligate intracellular parasites.
• Viruses disrupt normal host cell function by using host metabolic systems

Virus Features

• Viruses are filterable disease-causing agents
• They lack a plasma membrane (acellular)
• They contain a single type of nucleic acid, either DNA or RNA, but never both
• Viruses are surrounded by a protein coat called a capsid
• They may or may not possess an additional envelope of lipids or proteins.
• They have very few of their own enzymes, relying instead on host enzymes

Host Range

• Viruses can infect animals, plants, fungi, protozoa, and bacteria
• Most viruses are specific to a single host species
• To infect a cell, a virus must recognize particular surface features on the host cell, such as HIV recognizing the CD4 receptor on human immune cells

Viral Size

• Viruses are very small and viewed with an electron microscope
• Viruses range in length from 20-1000 nm

Structure of Viruses: Nucleic Acids

• A virus has either DNA or RNA as its genetic material, but not both
• The genetic material can be single-stranded or double-stranded (dsDNA, ssDNA, dsRNA, ssRNA)
• Nucleic acid can be linear or circular
• It can also be segmented and arranged in many pieces.
• The total amount of nucleic acid varies from a few thousand to 250,000 base pairs, compare to E. coli chromosome which contains 4,000,000 base pairs

Capsid

• A capsid is a protein coat surrounding the nucleic acid
• It is made up of individual proteins called capsomeres and provides the virus with its shape
• The arrangement of capsomeres is characteristic of a particular virus
• The nucleocapsid, which is the nucleic acid and the capsid together, is the minimal structure required for a virus

Envelope

• The envelope is not present in all viruses
• If present, the envelope is a lipid bilayer (membrane) acquired from the host cell.
• It functions as the external coating around the nucleocapsid
• Additional viral proteins, called spikes, may be inserted into the envelope

Virus Morphology

• Virus morphology is based on the shape of the capsid
• Helical viruses have long rods that can be rigid or flexible
• Polyhedral viruses are usually icosahedral, with 20 triangular faces and other geometric shapes possible
• Enveloped viruses are roughly spherical, with their shape dictated by the lipid bilayer

Complex Viruses

• Complex viruses have a complicated structure
• They may have additional protein structures attached to the capsid
• Complex viruses are common in bacteriophages, which are viruses that infect bacteria

Classification of Viruses

• Viruses are classified based on nucleic acid type, which are DNA or RNA (not both)
• Strandedness can be single or double
• Arrangement is either a segmented chromosome or a single molecule
• Viruses are classified based on capsid structure which can be polyhedral or helical
• Finally classified based on Envelope presence which can be either present or absent

Naming of Viruses

• Virus families end with the suffix "viridae" (e.g., Retroviridae)
• Genus ends with the suffix "virus" (e.g., Lentivirus)
• Species-specific endings are not used, instead, viral species are given a descriptive name, such as Human Immunodeficiency Virus (HIV)

Multiplication of Animal Viruses

Adsorption

• The virus attaches to the host cell
• Attachment is facilitated by attachment sites that are proteins or glycoproteins within the host membrane that the virus recognizes

Penetration

• Entry into the host cell
• Naked viruses enter the host cell via endocytosis
• Some enveloped viruses enter the host cell with the lipids of the envelope fusing with the host cell plasma membrane

Uncoating

• The viral nucleic acid separates from the capsid

Biosynthesis

• Host metabolic enzymes are used in this stage
• The viral nucleic acid replicates
• DNA replication occurs in the nucleus of the host cell
• RNA replication occurs in the host cytoplasm
• Viral proteins are synthesized in the cytoplasm for both DNA and RNA viruses, and capsomeres are constructed

Maturation and Assembly

• New virus particles assemble from nucleic acids and capsomeres
• Nucleocapsids are formed

Release

• Naked viruses burst out of the host cell, causing the cell to rupture and die
• Enveloped viruses bud out of the host cell, pushing through the plasma membrane
• The envelope forms from the plasma membrane
• This results in a steady release of mature enveloped viruses over time, and the host cell remains alive for a long time

Interactions Between Viruses and Animal Hosts

• Host defenses play a major role in the outcome of viral infections
• The host defense protects against an otherwise lethal infection
• Most healthy humans carry viruses and antibodies for viruses
• If a virus transfers from an immune host to another individual, it can result in infection

Types of Infection

Acute Infections

• Usually very short in duration
• Disease symptoms result from tissue damage
• Lysis of the infected host cells causes the release and spread of virus particles
• The host defense system gradually eliminates the virus over days or months
• The host may or may not develop long-lasting immunity
• Examples include Measles, Mumps, and Influenza

Persistent Viral Infections

• Virus particles are continuously present in the body and released from infected cells by budding
• Persistent infections may or may not cause disease; there may be no symptoms

Subgroups of Persistent Infections:

• Acute infection followed by late complications
• Chronic infection
• Slow infection
• Latent infection

Acute Infection with Late Complications

• Virus particles can persist after the acute infection period and gradually increase over a period of years, causing serious disease years later
• Example: Measles can lead to subacute sclerosing panencephalitis (SSPE), a rare but fatal brain disorder that occurs in 1 in 300,000 people up to 10 years after the initial measles infection

Chronic Infections

• Infectious virus is present at all times, and disease may or may not be present
  • Example: Hepatitis B is transmitted either sexually or via the blood. It may have an acute period with fever, nausea, and jaundice, and can eventually cause cirrhosis or cancer of the liver.

Slow Viral Infections

• After the initial infection, the amount of virus present increases over a very long period
• The initial infection is followed by an asymptomatic period
• Results in a very slow, progressive disease.
  • Example: HIV accumulates over a number of years, and is transmittable following the initial infection
  • HIV eventually develops into Acquired Immunodeficiency Syndrome (AIDS)

Latent Viral Infections

• The acute infection is followed by an asymptomatic period and the disease can be reactivated years later
• The symptoms may be different when reactivation occurs
• Example: Varicella Zoster Virus (VZV), which is in the Herpes family, causes chicken pox in children, remains latent for years without any disease, and can reactivate later in life to cause Shingles

Viruses and Cancer

• Viral DNA can transform normal animal cells into malignant cancer cells
• Only certain viruses have this capability
• Normal animal cells have genes called proto-oncogenes, these genes are required for normal growth
• When mutations occur in these genes, they become oncogenes
• Resulting in uncontrolled cell growth and tumor formation and can occur as a result of mutagens (carcinogens)
• Oncogenic viruses have viral DNA inserted into host cell chromosomes may have oncogenes present in the viral DNA
• They can also cause proto-oncogenes to be over-expressed, leading to an increase in transcription
• This over-expression results in the proto-oncogene becoming an oncogene

Possible Oncogenic Viruses

• Human Papilloma Virus (HPV) is a sexually transmitted infection
• It causes genital warts, believed to cause almost all cases of cervical cancer
• Epstein-Barr Virus (EBV) causes infectious mononucleosis
• It may cause lymphoma (White blood cell cancer) and some cancers of the nose and throat
• Hepatitis B Virus (HBV) is believed to cause many cases of liver cancer

Virus-like Infectious Particles

Viroids

• These are single pieces of RNA that are naked, with no protein coat
• Cause plant diseases, but are not yet found in animals

Prions

• Infectious protein particles that contain no genetic material (DNA, RNA)
• They are linked to several fatal human and animal diseases, such as Transmissible Spongiform Encephalopathy (TSE)
• Brain function degenerates as neurons die, forming "sponge-like" holes in brain tissue

Mode of Prion Infection

• Prions are most frequently carried in food
• Sheep infected with prions (Scrapie) can infect cows (Mad Cow Disease) who consume the sheep
• Humans that consume the meat of the infected cows develop Variant Creutzfeld-Jakob Disease
• Prions are resistant to high temperatures but can be destroyed by autoclaving in a solution of sodium hydroxide, which makes the beef inedible
• The onset of disease in humans occurs several years after infection
• It is not clear how or why this protein accumulates in the brain
• Prion disease is always fatal, and there is no treatment or cure

How a Single Protein Can Be Infectious

• Genes create normal protein, called NP
• NP does not normally cause any harm and has no known function
• PP (prion protein) is in a different form
• PP converts NP into a prion protein shape and converts it into PP shape
• The result is disease