Virus Notes

Introduction

•       Louis Pasteur postulated that rabies was caused by a virus (1884)

–      Developed first vaccine for rabies

•       Ivanovski and Beijerinck showed a disease in tobacco was caused by a virus (1890s)

•       1950s virology was a multifaceted discipline

–      Viruses: noncellular particles with a definite size, shape, and chemical composition that can be a poison

–      Can infect every type of cell

•       Animal, bacteria, plants, fungi, protist

Virus Size (small-ultramicroscopic!)

General Characteristics of Viruses

•       Viruses are non-living entities that are bits of nucleic acid surrounded by a protein coat.

•       They can only replicate inside living cells (obligate intracellular parasite).

•       Bacteriophage (phage): viruses that infect bacteria

Viral Architecture

•       Viruses bear no resemblance to cells

–      Lack protein-synthesizing machinery

–      Infectious particles that are active or inactive

–      Viruses contain only the parts needed to invade and control a host cell

- These never have DNA and RNA. It’s either one or the other

•       Viruses are surrounded by a protective protein coat called a capsid.

•       The capsid protects the nucleic acid when the virus is outside of the host cell

•       The viral capsid together with the nucleic acid is called the nucleocapsid.

•       Some viruses have an external covering called an envelope.

•       helps the virus bind to a cell surface and assists the penetration of the viral DNA or RNA into a suitable host cell

•       Capsid and envelope stimulate host’s immune system-antibodies

•       Those lacking an envelope are called naked.

•       Viruses can have a relatively simple shape which show icosahedral symmetry (20 sides with 12 corners)

•       Viruses can also be helical in shape, giving the virus a filamentous or rod-like appearance.

•       Viruses can also be complex in shape, some having an icosahedral head (capsid) with a long, helical protein component called the sheath, tail pins, and tail fibers.

The Viral Genome (genetic information expressed through DNA, RNA))

•       Viruses contain only a single type of nucleic acid – either DNA or RNA – but never both.

–      Genetic material carry information for viral structure and function

–      Genome: the sum total of the genetic information carried by an organism

•       Carries genes necessary to invade host cell and redirect the host cell’s activity to make new viruses

•       Number of genes varies for each type of virus – few to hundreds

Replication Cycle

•       Viruses can only multiply in living cells because they lack the cellular components necessary for harvesting energy and synthesizing proteins.

•       Because of this they are called obligate intracellular parasites.

•       Viruses must possess the genetic information to encode proteins required to:

1.      Make the viral protein coat

2.      Replicate viral nucleic acid

3.      Move the virus in and out of the host cell

•       Invasion: Virus encounters a susceptible cell

        Binds to specific receptors on the host cell membrane

•       Enveloped viruses- glycoprotein spikes bind to receptors

•       Naked viruses have surface receptors on capsid that adhere to receptors

Must bind to receptor exactly, therefore certain viruses will only “attack” certain cells

•       Cells that lack compatible virus receptors are resistant to adsorption and invasion by that virus

Bacteriophage Replication

•       Bacteriophages – bacterial viruses (phages)

•       Most widely studied are those that infect Escherichia coli

•       Multiplication goes through similar stages as animal viruses

•       Only the nucleic acid enters the cytoplasm (see next slide)

•       Release from host cell is a result of cell lysis induced by viral enzymes and accumulation of viruses - lytic cycle

•       Lytic phage multiply inside the cells they invade then escape by lysing (bursting) the host cell.

•       This process is called a productive or lytic infection.

•       Temperate phage integrate their DNA into the host’s genome and replicate when the host replicates.

•       Temperate phage do not lyse the cell

Stages of phage replication

1. Adsorption – binding of virus to specific molecules on host cell

The protein fibers at the end of the phage tail attach to specific parts of the bacterial cell wall.

                   The base plate with tail spikes settle on the surface of the bacterium.

2. Penetration – genome enters host cell

An enzyme at the tip of the phage tail degrades a small portion of the bacterial cell wall and the tail opens.

The DNA passes through the open channel of the phage tail and is literally injected into the interior of the cell.

3. Replication – viral components are produced

Phage DNA is “read” (transcribed), producing mRNA which is then “made” (translated) into the phage-encoded proteins.

Genetic material is replicated using host machinery.

4. Assembly – viral components are assembled

5. Maturation – completion of viral formation

6. Lysis & Release – viruses leave the host cell to infect other cells

During the late stages of protein production the phage-encoded enzyme lysozyme is synthesized.

Lysozyme is responsible for digesting the host cell wall from within, resulting in cell lysis and the release of phage.

Lysogeny: the silent virus infection

•       Not all phages complete the lytic cycle

•       Some DNA phages, called temperate phages, undergo adsorption and penetration but don’t replicate or lyse the host cell

•       The viral genome inserts into bacterial genome and becomes an inactive prophage – the cell is not lysed

•       Prophage is retained and copied during normal cell division resulting in the transfer of temperate phage genome to all host cell progeny – this is called lysogeny

•       Lysogeny results in the spread of the virus without killing the host cell

•       Induction can occur resulting in activation of lysogenic prophage followed by viral replication and cell lysis

•       When bacterium acquire viral DNA, it can increase the pathogenicity of the bacterium

–      Result in bacteria that are more virulent

–      production of toxins or enzymes that the bacterium would not otherwise have

Animal Viruses

•       Structure: Capsid proteins, nucleic acid (DNA or RNA), spikes, may or may not have a viral envelope.

•       Spikes can be found on naked or enveloped viruses:

•       Project from the nucleocapsid or the envelope

•       Allow viruses to dock with host cells

Classification

1. Genome Structure – DNA or RNA, single or double-stranded, a single molecule or segmented

2. Virus Particle Structure – icosahedral, helical, pleomorphic (irregular shape)

3. Presence or absence of a viral envelope

The Phases of Animal Virus Replication

1. Adsorption: Through their spikes, animal viruses bind to very specific receptors on the host cell surface (host range). Virus’s must attack for absorption

2. Penetration: For a virus to enter it must penetrate the host cell membrane (by membrane fusion or endocytosis – see next slide). genome enters hosts cell

3. Uncoating: Once inside the cell, the virus is uncoated (capsid removed) and the nucleic acid is released. viral componets are produced but it doesn’t happen in bacteriophage.

4. Synthesis: Critical viral proteins are synthesized and genetic material is replicated.

5. Assembly: Mature virus particles are constructed from the growing pool of viral parts (RNA, capsomers, spikes). Viral componets are assembled

6. Release: Assembled viruses leave their host by either cell lysis (bursting) or budding/exocytosis (enveloped viruses only).

Budding does not necessarily kill the host cell.

Extracellular virus product is virulent ( capacity to harm host cell) is a “virion”

Viral DNA becomes the prophage

Damage to Host Cells

Cytopathic effects - virus-induced damage to cells

1. Changes in size and shape

2. Cells fuse to form multinucleated cells

3.     Cell lysis

4. Alter DNA

5. Formation of inclusion bodies

6.     Mass of virus or damaged organelles

7.     Transform cells into cancerous cells

Persistent Infections

•       In persistent infections, the viruses or their genomes are continually present in the body, so this is what lysogeny was in bacteriophage.

•       Virions are released from infected cells by budding (not lysis).

•       Can last weeks or host’s lifetime; several can periodically reactivate

•       Persistent infections may or may not cause disease, however since the virus is always present the host is called a carrier.

There are 3 major categories of persistent infections:

1.      Latent infections: persistent infections in which a symptomless period is followed by reactivation of the virus with accompanying symptoms.

Infectious particles cannot be detected until the disease is reactivated.

2.      Chronic infections: In chronic infections, the infectious virus can be detected at all times.

•       Symptoms may be present or absent during an extended period of time.

3.     Slow infections: , following the initial infection, the infectious agent gradually increases in amount over a very long time during which no symptoms are apparent.

Eventually, a slowly progressive lethal disease occurs.

Viruses and tumors

•       Some animal viruses enter the host cell and permanently alter its genetic material resulting in cancer – transformation of the cell

•       Transformed cells have an increased rate of growth, alterations in chromosomes, and the capacity to divide for indefinite time periods resulting in tumors

Medical Importance of Viruses

•       Viruses are the most common cause of acute infections

•       Several billion viral infections per year

•       Some viruses have high mortality rates

•       Possible connection of viruses to chronic afflictions of unknown cause

Detection and treatment

•       More difficult than other agents

•       Take appropriate sample

–      Infect cell culture – look for characteristic cytopathic effects

•       Requires cell culture or tissue culture method

–      Screen for parts of the virus-antigen

–      Screen for immune response to virus (antibodies)

–      Antiviral drugs can cause serious side effects

Prions

•       Composed primarily of infectious protein (no nucleic acid)

•       Exact mode of infection is still being investigated

•       Deposited as long protein fibrils in the brain tissue of humans and animals:

–      Creutzfeldt-Jakob disease: afflicts the central nervous system and causes degeneration and death

–      Bovine spongiform encephalopathy (“mad cow disease”)

–      Shy-Drager syndrome or multiple system atrophy resembles Parkinson’s disease

Oncovirus : tumors

• papillomavirus

• herpesvirus

• Hepatitis B. virus