Viruses and Prions

Transmission electron micrograph of noroviruses.
Transmission electron micrograph of shape of norovirus particles (virions). Noroviruses cause the “stomach flu” or gastroenteritis. Content provider: CDC/Chales D. Humphrey http://phil.cdc.gov/phil/details.asp

How can such simple structures be so puzzling? Compared to the multi-system complex vertebrates made up of organized cells, tissues, and organs, viruses and prions appear, at first glance, to be extremely simple particles – such as this prickly flu virion to left. But, appearances are deceiving.

With seemingly very little to work with, viruses and prions cause debilitating conditions and countless deaths from diseases that cannot be cured and that science struggles to control. How can virus and prion disease effects be so destructive?

Objectives

To understand the importance of viruses and prions, you should be able to:

  • Compare and contrast the structure and characteristics of different types of viruses.
  • Explain why scientists have not agreed on the classification of viruses as either living or non-living.
  • Describe diseases caused by different types of viruses.
  • Describe the structure of a prion.
  • Explain how viruses replicate.
  • Explain the significance of prions in causing infectious disease.

 

Vocabulary

bacteriophage—a virus that attacks bacteria.

capsid—the protein shell of a virus which encloses the genetic material.

coronavirus—group of viruses named for the crown-like spikes on the surface of the enveloping protein coat; cause upper respiratory tract illnesses.

hemagglutinin (HA)—a protein on the surface of an influenza virus responsible for viral attachment to specific receptors on host cells.

host—an organism on which another organism lives.

lysogenic pathway—a latent, or inactive, phase of viral replication cycles; viral genes integrate into a host chromosome and stay inactive through many host cell divisions.                            

lytic pathway—a phase of rapid replication in viral replication cycles.

neuraminidase (NA)—a protein on the surface of an influenza virus that allows the virus to be released from the host cell.

prion—small proteins that are altered gene products that cause degenerative diseases of the nervous system.

virology—the study of viruses.

virus—an infectious agent consisting of genetic material (DNA or RNA) and a protein coat.

Viral Structure  

Diagram of the structure of an influenza virus.
Model of an influenza virus. Credit: NIH

Viruses are made up of a protein coat, or capsid, which encloses either DNA or RNA, the genetic code for the virus. Some viruses also have a membrane (made up of lipids) that covers the capsid, but not all viruses have this membrane.

   Other features of some viruses make them very well adapted for causing disease. The features are not additional components; they are part of the protein coat or viral genetic material. For example, the protein coat consists of one or more types of protein subunits arranged in various shapes, depending on the virus type. Some viral coats have spikes and tails. Spikes and tails help the virus bind to receptor sites on host body cells.

   Once inside the body cell, viral DNA or RNA can be replicated and thousands of new viral particles are produced. The host cell dies and the new viral particles infect more host cells.

 Viral Infection and Replication

   Once inside the body, viruses are able to infect cells and cause disease. Viruses multiply slightly differently according to type, but almost all cycle through the same five steps:

1) Attachment:  The virus attaches to a host cell. Any cell will do as long as the virus can chemically attach to specific molecular groups on the cell surface.

2) Penetration: The entire virus or just its genetic material penetrates the cell and enters the cell’s cytoplasm.

3) Replication and Synthesis: The viral DNA or RNA uses the host cell to produce thousands of copies of viral nucleic acids and proteins.

4) Assembly: The new viral nucleic acids and proteins form new viral particles.

5) Release: New viral particles are released from the cell, the cell dies, and the new particles go on to infect other healthy host cells.

   These five basic steps take place in all viral replication, but different viruses accomplish them in slightly different ways.  Some viruses enter the host nucleus and use the cell’s structures to replicate, but stay separate from the cell’s genetic material. Adenovirus is an example of a DNA virus that replicates in this way; influenza is an example of an RNA virus that also uses the cell’s structures to make RNA copies of itself but stays separate from the host cell’s genome.

   Retroviruses replicate in a slightly different way. They are RNA viruses but the RNA is converted into DNA by a viral enzyme, reverse transcriptase. Once the RNA has been converted into the double-stranded DNA, it can become part of the host cell’s (DNA-based) genome. The virus goes on to replicate using the cell’s structures.

   Human Immunodeficiency Virus (HIV), the common cold, and some forms of cancer are retroviruses. Most retroviruses are associated with causing lifelong infections.


Bacteriophages  

 Now, consider the bacteriophages—a group of viruses that infect bacterial cells. Much of what we know about viruses come from our study of bacteriophages. Bacterial cells can be cultured easily and quickly in a laboratory and are used in initial testing of viral characteristics.

Electron micrograph of bacteriophages (small round structures) and bacterium
Electron micrograph of bacteriophages attached to a bacterial cell. Image: Dr. Graham Beards. https://en.wikipedia.org/wiki/Bacteriophage#/media/File:Phage.jpg

   Bacteriophages replicate using the same basic steps as outlined above, but can also have slightly different pathways.   The lytic pathway for bacteriophages is the rapid replication that ends with lysis of the host cell.  Some bacteriophages also have a lysogenic pathway. In this pathway, viral nucleic acids integrate into the host chromosome and may stay inactivated through many host cell divisions. This produces a latent period that extends over many replication cycles.

Cure you by giving you a virus?

Have you ever thought that one day doctors may cure your bacterial disease by injecting you with a virus? Before you say no to that treatment, consider all the facts.

It has to be a specific type of virus. It has to be a bacteriophage—a virus that attacks and replicates inside bacteria. Some bacteria are attacked by viruses that take over the bacterial cell and use it for replication. 

The bacteriophages inject their DNA or RNA genetic code into the bacterium cytoplasm and replicate. They take over the bacterial cell and make thousands of copies. When the bacteriophage copies burst from the cell, the bacterial cell dies, and new bacteriophages infect new bacterial cells.

These bacteriophages do not invade animal or human cells and are therefore, harmless to humans.

Bacteriophages are used as therapy in bacterial diseases. You can see why if you consider that the bacteriophage kills bacteria, but not their human hosts. It is considered especially promising since the numbers of antibiotic resistance bacteria are increasing dramatically.

Bacteriophage therapy has other advantages over more traditional antibiotic therapy. Phage are specific against the bacteria, but do not harm human cells and also do not harm the helpful bacteria in the body; antibiotics kill even the helpful bacteria in our bodies.

Viruses as Pathogens

A healthcare worker in protective gear uses safety procedures.
Healthcare worker observing safety protocols and protective gear when working with contagious viruses. Source: http://phil.cdc.gov/phil/details.asp

  Viruses are efficient pathogens.  You are probably already familiar with many of the diseases viruses cause and have probably been immunized against quite a few. Measles, mumps, chickenpox, and influenza are all viral diseases. Each viral disease has a characteristic transmission method and vectors (if any) and produces characteristic symptoms.  Many viral diseases have deadly consequences; three examples are briefly described here. More information about viral diseases that may be emerging or re-emerging diseases can be found in the Table: Global Emerging Diseases on the Pandem Disease Center site.

 Ebola

   Ebola, a deadly hemorrhagic disease, is a viral disease that was in the news for months during a recent outbreak in Africa.  American healthcare workers were infected with the Ebola virus and were brought back to the U.S. to receive extensive medical care. In another case, a visitor to the U.S. from west Africa brought the Ebola virus into Texas and infected healthcare workers here.

Image of Ebola virus
Electron microscope image of an Ebola virus. Image: https://en.wikipedia.org/wiki/Ebola_virus_disease

The disease is transmitted through contact with infected body fluids. Many people were infected through cultural burial traditions that involved contact with family members who died from Ebola. Thousands were infected as the pathogen spread among populations of several countries because proper epidemiological protocols were not followed. Ebola symptoms include fever, headache, weakness, diarrhea, vomiting, and hemorrhaging (uncontrolled bleeding) under the skin, in internal organs, and out body openings such as the mouth, eye, or ears.  Death usually occurs. 

   Ebola is not the only hemorrhagic disease. Dengue hemorrhagic fever and Marburg hemorrhagic fever are also grouped in one of the four families of viral hemorrhagic fevers (VHF). All are RNA viruses and all have a lipid coating.

   Health research institutes are working on vaccines for the hemorrhagic fevers, but there is no cure for viral diseases. But, there are vaccines for some diseases. A vaccine is a solution of dead or weakened disease-causing particles that stimulate the body’s immune system to produce antibodies. The antibodies, specific to the disease, later recognize the pathogen’s antigen and protect the body against the disease.

Influenza

Image of an influenza virion
Each year more than 200,000 people are hospitalized from flu complications and about 36,000 people die from it. Shown: an influenza virus. Credit: Frederick Murphy http://phil.cdc.gov/phil/details.asp

   Millions of people get the flu every year. While some people have mild illness, others have severe complications that can result in hospitalization or death.

   There are three types of influenza viruses: A, B, and C. Influenza types A and B cause human seasonal flu outbreaks almost every year. Influenza type C viruses cause only mild respiratory illness and do not cause widespread outbreaks or epidemics.

   Influenza Type A viruses have two surface proteins, hemagglutinin (HA) and neuraminidase (NA). Both are embedded in the lipid membrane of the viral envelope. Hemagglutinin is responsible for the attachment of the virus to specific receptors on a host cell surface and also facilitates the fusion of the viral envelope and the cell membrane. In this way, the virus can transfer its genetic material into the host cell. Neuraminidase is a protein on the viral surface that allows the virus to be released from the host cell after replication.

   There are different arrangements of both glycoproteins (hemagglutinin and neuraminidase) which result in different viral subtypes. Eighteen different hemagglutinin subtypes and 11 different neuraminidase subtypes have been identified. Different strains of these subtypes can also occur.  Types of influenza are identified by their H and N configuration. For example, the H1N1 virus caused an influenza pandemic in 2009.

   Influenza B viruses do not have HA and NA subtypes but are broken down into lineages. Examples are the B/Yamagata and the B/Victoria.

   Influenzas are named by a naming system accepted by the World Health Organization (and followed by the U.S. CDC) that takes into account multiple identification characteristics such as host of origin, geographic origin, strain, and year, but most flus are commonly referred to by their HA and NA numbers, such as H3N2 or H7N9. 

   Each year, a vaccine is produced after careful scrutiny and prediction of the influenza strains that may infect populations that year. The best way to prevent getting influenza is to get a flu vaccine.

Human Immunodeficiency Virus (HIV)

Image of HIV virion (small round green particles) and a lymphocyte (pinkish structure).
Scanning electron micrograph of HIV virions budding on a lymphocyte (white blood cell). Photo credit: C. Goldsmith. Image: http://phil.cdc.gov/phil/details.asp

   HIV is a contagious disease caused by a single-stranded RNA retrovirus. HIV attacks and gradually destroys the body’s immune system. It is considered a pandemic disease by the World Health Organization (WHO) and has killed over 25 million people worldwide. The number of people infected each year continues to increase.

   The virus is spread person-to-person through sexual contact, blood (predominantly from needle-sharing), and from mother-to-child during pregnancy or through breast milk. Infections by contaminated transfusions and blood products have been almost eliminated in developed countries by screening and testing that occurs before blood use.

   A person may have no symptoms for up to 10 years after being infected with HIV. He/she is, however, able to transmit the virus to another person. Some people have flu-like symptoms during this initial period after infection, but those symptoms pass. 

   After this initial phase, the person enters a stage called clinical latency during which there are no symptoms. HIV reproduces, but at very low levels. If he/she has tested positive for HIV and has started anti-viral therapy (AVT), he may be able to keep the viral load in his blood at low enough levels to not develop symptoms for up to 10 years. The patient is still able to infect other people with this disease.

   HIV progresses to Acquired Immunodeficiency Syndrome (AIDS). Symptoms include rapid weight loss, profuse night sweats, fatigue, swelling of lymph glands, diarrhea, sores, pneumonia, memory loss, depression, cancer, chronic wasting disease, dementia, and neurological disorders.

HIV is a death sentence. It can be treated to delay death, but it cannot be cured.

Note: Even though high profile viral diseases make the news, it doesn’t mean that viruses are more deadly than bacteria, prions, or any other type of pathogen. Each pathogen has specific characteristics; virulence depends on the specific pathogen

Living or Non-Living?

Image of a coronavirus (round structure in the middle) that causes MERS.
Transmission electron micrograph of the coronavirus that causes MERS (Middle East Respiratory Syndrome). Content Provider: NIAID http://phil.cdc.gov/Phil/details.asp

   Whether or not viruses are living has been questioned for decades. They have genetic material, they reproduce copies, and they evolve through natural selection. These are all characteristics of living organisms. However, they lack cell structure and they cannot reproduce outside a host cell. These two are also characteristics that scientists use to define life.

   Even though viruses have a seemingly simple structure, they come in a variety of shapes and can be quite distinctive in appearance. For example, the coronaviruses appear to have a halo surrounding the protein coat. They are helical and large for an RNA virus. The corona-like appearance results from protein spikes on the surface of the virus.

Prions

   Now let’s consider a pathogen even simpler than a virus. Prions consist only of protein, yet are the cause of fatal diseases. A prion protein has multiple folding patterns and is capable of causing abnormal folding of normal proteins found mostly in the brain. The abnormal folding leads to brain damage, neuron less, and neurodegenerative disorders. All prion diseases are fatal.

Most people had never heard much about prion diseases until “mad cow disease” made the news several years ago. As cows in the United Kingdom were found to be sickened with the disease, the U.S. cut off purchasing beef from the U.K. as a precaution. The disease can be transmitted to people when they eat beef contaminated with the prion.

Image of prions (red structures) with neurons (connected cells)
A neuron showing the presence of a prion protein (in red). Photo Credit: NIAID. Image: http://phil.cdc.gov/phil/details.asp

Examples of prion diseases include:

  • CJD (Creitzfeldr-Jakob disease)-This disease has an inherited form (familial CJD) and a non-inherited form. CJD symptoms quickly lead to severe disability and death.
  • Variant CJD-Related to “mad cow disease”, variant CJD is caused by eating diseased meat having the prion necessary to cause abnormal folding in the brain. The disease may also be spread from infected tissue transplants and contaminated medical equipment.
  • Kuru-Occurring in New Guinea, Kuru is spread by eating contaminated human brain tissue. Incidence of
  • kuru declined sharply once the transmission mechanism was identified.

   Since prions are neurodegenerative diseases, infected people experience muscular coordination problems, personality changes, impaired memory and thinking, and vision problems. They may eventually lose the ability to speak or move; coma can occur, leading to death.

Check Your Understanding

  1. Describe the structure of a virus.

 

 

 

 

 

 

  1. How does a virus cause disease in the human body?

 

 

 

  1. How does a virus multiply?

 

 

 

 

 

 

 

 

 

  1. Describe the structure of a prion.

 

 

 

 

  1. With respect to genetic composition, how are prions unlike any other type of infectious agent?