Viruses

What are they?How do they work?

Where do they come from?And… What good are they?

VirusesInfectious agents acting INSIDE cells

Key Concepts

• A virus has a genome but can reproduce only within a host cell

• Viruses, viroids, and prions are formidable pathogens in animals and plants

Viruses:

Make a Living by Hijacking Cells– Not living organisms; lack some attributes of

life.

– Are infectious particles, can’t replicate independently.

– Not cells and don’t carry out metabolism

– Made of RNA or DNA usually enclosed in protein coat (viroids lack protein coat).

Viruses• Consist of

– nucleic acid (dsDNA, ssRNA, dsRNA) and

– protein coat = capsid.

• Viral envelopes –in some allow them to infect host more efficiently – don’t lyse cell when new viruses are made

• Bacteriophage – bacterial viruses

Protein coat (capsid) takes many shapes.

DNA or RNA is always within the capsid

Some viruses have an envelope to cover them!

Envelope – came from host’s cell membrane when virus budded out of host

Some VIRUSES have no envelope – they’re naked! HERE IS A virus THAT INFECTS BACTERIA – It is called a bacteriophage.

Adenovirus Influenza virus

Photographer: Sebastian Kaulitzki | Agency: Dreamstime.com

foxnews.com

Causes colds Causes the flu

How Big are viruses?

Polio virus = 20 nanometers

20nm

1 nm – 0ne billionth of a meter!

3000 polio viruses fit across the diameter of a period at the end of a sentence in your book.

Viruses can’t reproduce on their own

•They must invade a cell.•Once inside a cell, they cause the

cell to make more viruses instead of their usual proteins.

•They are intracellular obligate parasites – they can’t do anything on their own.

Viral Life Cycles – Lytic

The lytic cycle demonstrates the steps that a virus takes in order to take over a cell.

The steps are:

1. Attachment

2. Injection

3. Replication

4. Assembly

5. Lysis

1

2

1

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5

Sometimes the virus doesn’t kill the cell right away and it becomes part of the cell’s genes.

If this happens, the virus DNA becomes a provirus and can become activated at any time (like a time bomb).(prophage in bacteria cells)

In the meantime, the provirus is passed on to all the offspring of that cell …. Maybe for many generations.

Viral Life Cycles - Lysogenic1. Virus binds receptor

site and injects nucleic acid.

2. Viral nucleic acid is incorporated into cells genome (crossing over) = prophage / provirus.

3. Every time cell divides it copies viral DNA as its own.

4. At some point, viral DNA leaves chromosome and enters lytic cycle.

When were viruses discovered?Viruses have apparently always been around.

However, it wasn’t until 1897 that a Dutch scientist named Beijerinck called an invisible agent that was smaller than bacteria a virus (Latin for poison). He was studying tobacco leaves that had been infected with what we now know as tobacco mosaic virus.

Classification of Viruses By Shape by Host type by function

Retroviruses attack a certain way.

DNA viruses attack another way.

Animal viruses

Plant viruses

How do Viruses Attach to Host cell?• Viral protein interacts w/ host cell surface receptor.

– Specificity of attachment allow viruses to infect one species but not another . This is why we don’t get the same diseases as our pets!

• May attach to all host cells or just on certain cell type(s):– Polio digestive tract – then moves to bloodstream and in

some cases nerve cells

– Rhinoviruses/Influenza respiratory tract cells

– Chicken Pox and Herpes viruses skin and nerve cells

– HIV Immune system and brain

Acute Infections – = short in duration with rapid recovery

• Virions (virus particles) usually remain localized and symptoms are typically short-lived. 

• The infected host cells will die upon release of new virions, resulting in cell and tissue damage. 

• The Host's defense mechanisms will likely eliminate the virus over a period of several  days or months. -often results in the host organism's immunity to future infection. 

• Examples of acute infections include measles, mumps, and influenza (the flu).  

Persistent Infections = viruses are continually present in the body

Types• Late complications following an acute

infection

• Latent

• Chronic

• Slow

Persistent Infections• Late Complications following a viral infection:

– Often persistent infections are actually the result of an acute infection. 

• Ex: measles exhibits short infectious and disease phases, yet late complications in one in 300,000 individuals results in a fatal brain disorder (Subacute Sclerosing Panecephalitis (SSPE).  The new condition is the result of a defective viral  replication with brain cells. 

• When present, SSPE usually occurs within 10 years of having the measles. • Progressive encephalitis can follow rubella infection

Persistent Infections cont’d:Latent infections• actual viruses cannot be detected until reactivation of the

disease occurs• "latent" because they exhibit a long non-infectious stage

between the original disease and the subsequent disease.  – Chicken pox and the shingles, both of which are caused by the same

virus: Varicella-zoster virus.  Shingles or "zoster" appears after the virus

becomes reactivated by unknown circumstances.  – Herpes virus (both herpes simplex type 1 and 2)  is another ex. of a

latent virus

Persistent Infections cont’d:

• Continuous "chronic" infection follows a relatively brief disease stage. 

• virus can be demonstrated in the body at all times

• Examples of chronic infections include hepatitis B and C.  – Initial symptoms may include nausea, fever, and

jaundice; however, the patient typically recovers but remains infectious. 

– Over time the disease slowly manifests as hepatitis, cirrhosis of the liver, or cancer.   

SLOW Infections

• infectious agents gradually increase in number over a very long period of time during which no significant symptoms are seen. (Not the same as Chronic)

• Examples include HIV/AIDS, and prion diseases (even though they are not viral)

Remember this??

• DNA RNA Protein

in nucleus nucleuscytoplasm cytoplasm

^ ^

Transcription Translation

RNA Viruses Ex = influenza, polio, HIV

• Three types of replication– 1. RNA of virus is used directly as an mRNA encodes

all enzymes and proteins required. – 2. Contain enzyme that copies viral RNA into a

complementary strand that then acts as mRNA– The most famous example of RdRP is the Polio virus.– Also influenza 1,2,and 3 (RdRP =RNA dependent RNA

Polymerase)– 3. Retroviruses – are packaged w/ enzyme Reverse

Transcriptase that transcribes DNA from an RNA template so they can infect animal cells.

HIV = human immunodeficiency virus

On Retroviruses: The Violoist’s Thumb by Sean

Kean

“They show no respect for the Maginot Line we’d prefer to draw between ‘their’ DNA and ‘our’ DNA.”

Why do some viruses concvert RNA DNA after infecting cells: “DNA is sturdier, more enduring. Once these retroviruses so named because they run the DNA RNA Protein dogma backward – weave themselves into a cell’s DNA, the cell will faithfully copy the virus genes so long as they both shall live”

RetrovirusesRNA viruses

When infecting a cell, these viruses have to transcribe the RNA to DNA before the viral code can be read.

This requires an enzyme, reverse transcriptase, to Change RNA to DNA then the viral code can be added to the cell’s DNA.

Once part of the cell’s DNA, the viral code can cause the cell to make more viruses.

HIV IS A RETROVIRUS

Gp120 & gp41

envelope

HOW HIV GETS INTO A CELL

HIV IN A CELL AND BUDDING OUT OF A CELL

HIV infecting a T cell

HIV LIFE CYCLE HHMI Animation

http://www.hhmi.org/biointeractive/media/hiv_life_cycle-lg.mov

Ways to get HIV

Dirty needles Blood transfusions

At birth from mother

Unprotected sex

Immune response

free antigens in blood antigens on infected cells

humoral response cellular response

B cells T cells

macrophages(APC)

helperT cells

plasmaB cells

memoryB cells

memoryT cells

cytotoxicT cells

YYY

Y

YY

Y

YantibodiesY

Y Y

skinskinpathogen invasion

antigenexposure

HIV/AIDS

•Chronic attack on Helper T-cells of the immune system from initial acute infection (when patient has flu-like symptoms) until full blown immune deficiency which appear many years later

•HIV remains localized in lymph nodes for years until Helper T-cells are depleted there, then moves into blood where its T-cell numbers drop and immune function is debilitated.

•Rapid mutation –fastest known among the viruses! so fast that each variety cannot be characterized •Mutation is so great that vaccines cannot be made of noninfectious viruses – even killed virus, for fear that one may live or a mutation will make the virus active

T-cell count as disease progresses

HIV kills off Helper T-Cells

• T-cells are a crucial type of immune cell .

• HIV infections target these cells – specifically CD4 “Helper”T-cells

• Many Helper T-cells self destruct – apoptosis – see article 2010 article:http://www.biologynews.net/archives/2010/11/26/deciphering_how_cd4_t_cells_die_during_hiv_infection.html

By 2020 – predictions are that…

• HIV/AIDS will kill more people than any other disease outbreak in history.

• As many as 1 billion/yr (1 in 6 people)

• 70% cases occur in Africa – but it is not limited to 3rd world countries!

TREATMENT INCLUDES INHIBITORS OF ENZYMES:

1. Reverse transcriptase inhibitorThis enzyme allows viral RNA to code for DNA

2. Protease inhibitorThis enzyme allows viral proteins to be cut and fit

into the final virus

3. Integrase inhibitorThis enzyme allows the virus DNA to join the

cell’s DNA in the nucleus

Drug-resistant HIV

Cancer Causing Viruses

• About 20% of cancers seem to be caused by viruses.First identified in Chickens…Rous Sarcoma Virus….

“One great strategy for the viruses to spread like mad was to convince the cells harboring viral DNA to spread like mad too. The viruses did this by disrupting the genetic governors* that prevent cells from dividing rapidly. A runaway tumor was the result.” The Violinist’s Thumb, Sean Kean

*Those ‘governors’ are the genes that control cell division.

Tumor Viruses

• Tumor: uncontrolled growth of a single cell producing a mass of undifferentiated cells.

• Can be due to viral infection:– Viral genome inserts into eukaryotic host

genome– Forces host to replicate viral and host DNA

more than normal disrupts host cell’s ability to control cell cycle. tumor

DNA viruses that cause cancer:•Human Papilloma Virus (HPV) causes transformation in cells through interfering with tumor suppressor proteins such as p53.. Interfering with the action of p53 allows a cell infected with the virus to move into a different stage of the cell cycle, enabling the virus genome to be replicated. Forcing the cell into the S phase of the cell cycle could cause the cell to become transformed. Some types of HPV increase the risk of cervical cancer.

•Kaposi’s Sarcoma Herpes Virus is associated with Kaposi’s Sarcome, a type of skin cancer often seen in AIDS patients.•Epstein Barr Virus is associated with four types of cancers

RNA viruses•Hepatitis C Virus as well •Human T-Lymphotrophic Virus (HTLV-1).

Tree man…. Infected with HPV•his affliction is caused by the Human Papilloma Virus (HPV), a fairly common infection that usually causes small warts to develop on sufferers. •Dede's problem is that he has a rare genetic fault that impedes his immune system, meaning his body is unable to contain the warts. •The virus was therefore able to "hijack the cellular machinery of his skin cells", ordering them to produce massive amounts of the substance that caused the tree-like growths known as "cutaneous horns" on his hands and feet.

http://www.telegraph.co.uk/news/worldnews/1569156

Viruses infect many organisms, including bacteria, plants, and animals; cause much agricultural loss, mild to deadly human diseases (cold, flu, chickenpox, herpes, rabies, AIDS, some types of cancer).

ebola

polio

flu

smallpox

Aren’t you glad we don’t get smallpox anymore? Smallpox has been eliminated from the world as a result of immunizations

Vertebrates defend against viruses through: antibody-based immunity or cellular immunity.

1. Immune system produces specific proteins (antibodies) that recognize and bind viral particles, thereby blocking their replication.

2. Immune cells called T cells recognize and destroy cells harboring viruses (cellular immunity).

3. After first infection, body retains clones of antibody or T cells directed against that viral strain:Rapid defense is mounted upon second infection. This is what happened when you recovered from chicken pox.

This immune memory is the basis of vaccination;

A vaccine consists of killed or nonfunctional infectious agents or parts of those germs that trigger an immune response in body without causing disease symptoms. Upon subsequent infection with active virus or bacteria the body can then launch a rapid attack against the pathogen and prevent disease.

Dr. Edward Jenner produced the first vaccine that was used widely. He injected cowpox pus into a boy (His son!); the boy got cowpox and recovered.

Jenner then injected the boy with smallpox pus and waited…..the boy did not get smallpox.

Vaccines early warning for immune system

AIDS VACCINE? Not yet

• http://www.iavi.org/

• See this site for info on current breakthroughs in AIDS/HIV

Antiviral Drugs

• Unlike most antibiotics, antiviral drugs do not destroy their target pathogen; instead they inhibit their development.

• Designing safe and effective antiviral drugs is difficult, because viruses use the host's cells to replicate.

• The trick is to find targets for the drug that would interfere with the virus without also harming the host cells.

• Moreover, the major difficulty in developing vaccines and

anti-viral drugs is due to viral variation.

What do antivirals target?• "targets" should different from any proteins

or parts of proteins in the host or humans cells.

1. Blocking entry of virus into cells• Create a molecule that mimics the receptor protein

in order to tie up the virus particles

• Create a molecule that attaches to the cell receptor a virus would use to block it from the virus.

2. Destruction of viral proteins, or parts of proteins such as enzymes critical to viral reproduction.

– Reverse transcriptase– Integrase- helps viral DNA splice into host DNA– Destroying RNA produced from viral DNA– Protease – processes viral proteins for packaging

3. Prevention of viral assembly (Rifampicin)

4. Preventing release of viral particles from cell– (Tamiflu). Tamiflu binds to the active site on

neuraminidase protein, so that the virus can't leave the cell to infect other cells. Eventually, the virus dies. (The N part of H1N1)

Human diseases caused by viruses

• Common cold• Influenza (flu)• Chickenpox• Polio• HIV• Some pneumonia• Some meningitis• herpes

Influenza

• How you get the flu– http://www.pbs.org/wnet/secrets/features/killer-

flu/caught-the-flu/220/

• Historical video – flu – 55 min

– http://www.pbs.org/wnet/secrets/episodes/preview-of-killer-flu/222/-flu/caught-the-flu/220/

Nonviral infectious agents

• Prions– PIECE OF PROTEIN– CAUSE OF MAD-COW

DISEASE – CAN INFECT ANIMALS

– INCLUDING HUMANS

• VIROIDS– Single strand of

RNA– Causes plant

diseases

Proteins that corrupt other proteins =

Prions• Prions are

– Rare– Incurable– Take years for symptoms to appear =

• SLOW INFECTION

– Attack nervous tissue – Found in livestock – sheep and cows – but can

be transferred to humans through meat containing contaminated tissue.