Chapter 6 Objectives:
An Introduction to the viruses

• Looking for viruses
• What position do viruses hold
• Structure of viruses
• Classification of viruses
• How do viruses multiply
• How to cultivate and Identify viruses
• How viruses can be important in medicine
• Prions and other nonviral infectious particles
• How to detect and treat animal infections

History of Vaccination
Edward Jenner, Sarah Nelmes, and Smallpox
Louis Pasteur, Charles Chamberland, and Chicken Cholera
Louis Pastueur Rabies and Anthrax. Also he purposed the name "virus" (Latin for Poison)






PROPERTIES OF VIRUSES

• Are obligate intracellular parasites of bacteria, protozoa, fungi, algae, plants, and animals. Ultra-microscopic size, ranging from 20nm up to 450nm (diameter).
• Are not cells; structure is very compact and economical.
• viruses infect all known life forms
• viral DNA can sometimes become part of your own DNA
• viruses are incapable of replicating outside of a host cell
• viruses are host specific about which types of cell the infect
• The first time it was realized that viruses are so small that they can pass through a ceramic filter was with the tobacco mosiac model
• Do not independently fulfill the characteristics of life.
• Are inactive macromolecules outside of the host cell and active only inside host cells.
• Are geometric; can form crystal-like masses.
• Basic structure consists of protein shell (capsid) surrounding nucleic acid core.
• Nucleic acid can be either DNA or RNA but not both.
• Nucleic acid can be double-stranded DNA, single-stranded DNA, single-stranded RNA, or double-stranded RNA.
• Those that infect bacteria are more complex in shape than those that infect humans
• Molecules on virus surface impart high specificity for attachment to host cell.
• Viruses are usually only able to attack one kind of cell
• Multiply by taking control of host cell's genetic material and regulating the synthesis and assembly of new viruses.
• Lack enzymes for most metabolic processes.
• Lack machinery for synthesizing proteins.
• Most viruses are so small they require a electron microscope to see them.

Q: The main criteria used to group viruses are structure, chemical composition, and what other characteristic?
a. Area of host cell in which the virus multiplies
b. Similarities in genetic makeup
c. Presence and type of envelope

A: Similarities in genetic makeup




Flowchart of Virus

Virus particle

• Covering
  • Capsid
  • Envelope (not found in all viruses)

Central core

• Nucleic acid molecule (DNA or RNA)
• Matrix proteins (enzymes)

NAKED VIRUS:
Only has a capsid and nucleic acid.

Enveloped virus:
The virus has an envelope around its capsid


STRUCTURE OF VIRUSES:

I. Capsid:
- A shell that surrounds the nucleic acid in the central core of a virus. Together the capsid and the nucleic acid are referred to as the nucleocapsid.
- Made from a number of identical protein subunits called capsomers, which spontaneously self-assemble into the finished capsid.
- Capsomers arrange in two different shapes:
1) Helical:
- Rod-shaped capsomers that bind together to for a series of hollow discs resembling a bracelet.
- Influenza, measles, and rabies are enveloped helical viruses
2) Icosahedral:
- A 3-D 20-sided figure with 12 evenly spaced corners. Can look either ring or rod shaped.
- Papillomavirus is a naked icosahedron
- Herpes simplex virus is an enveloped icosahedron

II. Envelope:
- A covering external to capsid.
- Formed from a bit of membrane from the host's cell. Can come from the nucleus, endoplasmic reticulum, or cell membrane.
- Functions: 1) Protects the nucleic acid from the effects of various enzymes and chemicals when the virus is outside the host cell. 2) Also responsible for helping to introduce the viral DNA or RNA into a suitable host cell by binding to the cell surace and then assisting in penetration of the viral nucleic acid.

Side note: Yay for humans!:
- Parts of viral capsids and envelopes stimulate the immune system to produce antibodies that can neutralize viruses and protect against future infections.

Second side note: Complex/atypical viruses:
- More intricate in structure than the helical, icosahedral, naked, or enveloped viruses.
- Includes poxviruses: very large NDA viruses that lack a typical capsid. The agent of smallpox is a poxvirus.
- Includes bacteriophages: have a polyhedral capsid head and a helical tail and fibers for attachment to the host cell.

III. Spikes:
- Proteins that extend out from the envelope they are what allow the virus to bind with the host cell.
- Spikes are what the body recognizes as antigens to make antibodies against.

IV. Nucleic Acid:
- Genetic information carried by an organism. Viruses contain EITHER DNA or RNA but NOT BOTH!
- DNA is almost always double-stranded; RNA almost always single-stranded.
- Viruses have few genes:
* E. coli has about 4,000 genes
* Humans have 25,000-40,000 genes
* Mimivirus( the largest known virus) has thousands of genes and many of them qualify as living organisms.

Virions-mature virus particles


NAMING VIRUSES:

- No taxa above family (no kingdom or phylum/
- 19 families of animal viruses.
- Family name ends in VIRIDAE, ex. herpes viridae.
- Genus name ends in virus, ex. simplex virus
- Herpes simplex virus 1 (HSV- 1)

FAMILY= Herpesviridae
GENUS= Varicellovaries
COMMON NAME= Chicken Pox Virus
Disease= Chicken Pox

ANIMAL VIRUS MULTIPLICATION:

I. Adsorption:
- Attachment of capsid or envelope to cell surface receptors.
II. Penetration/Uncoating of Genome:
- Whole virus is engulfed and uncoated by the cell, or virus surface fuses with cell membrane; nucleic acid is released.
III. Replication and Maturation:
- DNA viruses usually replicate in the nucleus.
- RNA viruses usually replicate in the cytoplasm.
- Replication uses the host's cell machinery.
- Viral DNA or RNA is replicated and begins to function. Viral components synthesized.
IV. Assembly and Release:
- Assembled viruses leave their host in one of two ways:
1) Nonenveloped and complex viruses are released through cell lysis or rupturing.
2) Enveloped viruses are freed by budding or exocytosis from the membranes of the cytoplasm, necleus, endoplasmic reticulum, or the vesicles. Spikes on the enveloped viruses are inserted into the membrane.

Bacteriophage Multiplication

Adsorption: Precise attachment of special tail fibers to cell wall
Penetration: Injection of nucleic acid through cell wall; no uncoating of nucleic acid
Replication and Maturation: Occurs in cytoplasm. Cessation of host synthesis. Viral DNA or RNA is replicated and begins to function. Viral components synthesized
Viral Persistence: Lysogeny
Exit from Host Cell: Cell lyses when viral enzymes weaken it
Cell Destruction: Immediate



A single-stranded RNA virus (species Tobacco mosaic virus of the genus Tobamovirus) that occurs worldwide and causes mosaic disease in plants (as tobacco and tomato) especially of the nightshade family. This was the first virus to be shown to be so small that it would pass through a ceramic filter.

How Viruses Attack


Techniques in Cultivating and Identifying Animal Viruses:
Primary purposes of viral cultivation are:
1. To isolate and identify viruses in clinical specimen
2. To prepare viruses for vaccines
3. To do detailed research on viral structure, multiplication cycles, genetics, and effects on host cells.

Cell Culture Techniques
Makes it possible to propagate most viruses. Animal cell cultures are grown in sterile chambers with
special media that contain the correct nutrients required by animal cells to survive. They grow in a single sheet of
cells that supports viral multiplication.
Hela cells- Henrietta Lacks cancerous cells
Cancer cells are good for growing viruses, because you can maintain the cell line indefinitely.

Using Bird Embryos
Embryos are an intact and self supporting unit, complete with their own sterile environment and nourishment.
Several embryonic tissues readily support viral multiplication. Egg is inoculated through the shell. Signs of viral
growth include: death of embryo, defects in development, and localized areas of damage.

Live Animal Inoculation
Certain animals can propagate a given virus more readily than others. The animal is exposed to the virus by
injection of virus into the brain, blood, muscle, body cavity, skin, or footpads.

*Cannot grow on agar plate because a virus has no metabolism.


HIV/AIDS
More than 15 million children have been orphaned by AIDS, mostly African. To learn more about the immense difficulties faced by AIDS Orphans in Africa, visit this website.



Pathogenesis of the HIV virus: 1. HIV, covered with cell membranes, antibodies, and/or complement from the infected donor enters the new host. 2. Infecting virus is immunologically recognized as an "antigen complex" and, as such, is accosted by CD4-positive T-cells. Contact with protruding gp 160 results in infection of the cells. 3. The infected cell produces many more virions that are not coated with antibodies and are, therefore, able to freely produce a "spreading" infection among CD4-bearing cells. 4. Infected virus-producing cells shed antigens in the form of virions and viral proteins. These substances are immunogenic. 5. There is lymphoid hyperplasia accompanied by B-cell expansion and increasing levels of humoral antibodies and plasma cells. This is accompanied by a proportionate decrease in the numbers of circulating productively infected cells. This reciprocal change in virus-producing cells may either be due to cytotoxic T-lymphocytes or to virus inactivation by humoral antibodies or both. 6. There is an accumulation of HIV as a viral-immune complex on the surface of the cell membranes of follicular dendritic cells. This so-called "neutralized virus" is attached by Fc receptors on the cell surface. The virus reservoir is requisite for progression of the disease and virus concentrations of IXlO9 particles per cubic centimeter may be reached in the germinal centers. 7. The infected individual assumes a "steady state" of infection in which CD4 T-cells become infected as they migrate through the germinal centers. Depending on the amount of time from infection to activation and virus expression, infected cells produce virus particles in the lymphoid tissue or at distant sites elsewhere in the body. 8. The attrition of CD4 T-cells exceeds formation by a slight margin. This phase of the disease can continue for many years. 9. Due to the prolonged loss of T-cells and their functional interactions, the integrity and function of the lymphoid tissues are broached and there is loss of filtration of virus as well as global disorganization of the lymph nodes. Lymphoid tissues seem to depend on complex ecological interactions, modulated by cytokines and dependent on microenvironmental interaction. At some point in this process, the AIDS-defining stage is reached. 10. Immune function decreases until opportunistic AIDS-defining infections overwhelm the patient.
Much of what we know about viruses has come from the intense study of HIV. Here is an excellent animation of how the HIV virus infects CD4-positive T-helper cells, and what aspects of this infection can be treated with drugs. It is amazing how much is known about this process, and it is frightening (I think) to see it in action.




View the signs and symptoms of AIDS



This is off-topic somewhat. This is an Australian AIDS-awareness ad from 1986 (a time when the U.S. Government was hardly acknowledging the threat of HIV). Thanks to the wonders of the Internet, you too can see this disturbing ad.



Ebola
Ebola is a possible bio-weapon. It is highly contagious and infects mainly through contact transmission. If infected you will hemorrhage all over and bleed out. It has a very high mortality rate--what an unpleasant way to go.


Controlling epidemics
To hear the fascinating tale about the eradication of Smallpox, and how the lessons can be applied to prevent outbreaks of Bird Flu and other diseases, watch Dr. Larry Brilliant and his TED Talk.

Release of Mature Viruses

• nonenveloped and complex viruses that reach maturation in the cell nucleus or cytoplasm are released when the cell lyses or ruptures
• enveloped viruses are liberated by budding or exocytosis from the membranes of the cytoplasm, nucleus, endoplasmic reticulum, or vesicles
• budding of enveloped viruses causes them ti be shed gradually, w/o the sudden destruction of the cell wall
• regaurdless of how the virus leaves, most active viral infections are ultimately lethal to the cell membrane and organelles, toxicity of virus components, release of lysosomes
• the number of viruses released of virues bt infected cells is variable, controlled by factors such as the size of the virus and the health othe host cell
• about 3,000 to 4,000 virions are released from a tingle cell infected with poxviruses, whereas a poliovirus-infected cel can release over 100,000 virions. If even a small number of these virions happens to meet another suspectibvle cell and infect it, the potential for rapid viral proliferation is immense

Prions
misfolded proteins ( mad cow disease)

Viral infections

Molluscum Contagiosum-
An infectious, contagious viral infection of the skin caused by poxvirus. It causes epidermal cell proliferation forming sacules that contain clusters of the virus. Distribution on the skin is usually the trunk, face and extremities in children and pubic, genital, and perineal area on adults. Most lesions are self-limiting and clear in 6 to 9 months.

Rubella-
Caused by an RNA virus that enters the body via the respiratory tract. The incubation period is from 14 to 21 days. Prodormal symptoms include enlarged cervical and postaricular lymph nodes. A faint pink-red maculopapular rash develops on the face and trunk and spreads to the extremities in 1 to 4 days. There is no specific treatment. Supportive therapy includes rest, fluids and use of a vaporizer.


Rubeola (Red Measles)-
A highly contagious, viral disease in children. It is caused by an RNA containing paramyxovirus. It has an incubation period of 7 to 12 days. Prodormal symptoms include a high fever up to 40 degrees Celsius, malaise, enlarged lymph nodes, runny nose, conjunctivitis, and cough. Eurythematous maculopapular rash develops over the head, trunk, and extremities. Measles encephalitis occurs in 1 of 800 cases.

Varicella(Chicken Pox) & Shingles(Herpes Zoster)-
Are both produced by the varicella-zoster virus. It is a complex herpes group DNA. Incubation period is 10 to 27 days. Productive infection occurs within keratinocytes where vesicular lesions occur in the epidermis. The vesicle eventually ruptures and is followed by crust formation. Varicella occurs in people not previously exposed to VZV and herpes zoster occurs in partially immune individuals who have had varic' FONT adults.

SHINGLES




Louis Pasteur created some of the first vaccines for viruses, some of which include;Cholera Vaccine, Rabies Vaccine, and a Anthrax Vaccine. These vaccines were all produced by weakening the virus before injecting it into the host.

Mad Cow disease came from pirons.

A. Complex Viruses:
1. Poxvirus, a large DNA virus
2. Flexible-tailed bacteriophage
B. Enveloped viruses:
With a helical nucleocapsid:
3. mumps virus
4. rhabdovirus
With an icosahedral nucleocapsid:
5. herpesvirus
6. HIV (AIDS)
C. Naked viruses:
Helical capsid:
7. plum poxvirus
Icosahedral capsid:
8. poliovirus
9. papillomavirus


Questions

1. A virus is a tiny infectious
a. Cell
b. Living thing
c. Particle
d. Nucleic acid

2. Viruses that persist in the cell and cause recurrent diseases are considered
a. Oncogenic
b. Cytopathic
c. Latent
d. Resistant

3. Enveloped viruses carry surface receptors called
a. Buds
b. Spikes
c. Fibers
d. Sheaths

4. Viruses cannot be cultivated in
a. Tissue culture
b. Bird embryos
c. Live mammals
d. Blood agar

5. To be a virus you must have?
a. Capsids
b. Nucleic acid
c. Both a capsid and nucleic acid
d. Cell membrane

True or False:
6. A virus can have both, DNA and RNA.
a. True
b. False

7. The capsid of a virus is:
a. Made up of various phosholipids
b. Made up of glycalyx
c. Made up of protein based enzymes
d. Made up of individual protein subunits called capsomers

8. Bacteriophages are:
a. Bacteria that digest themselves
b. A virus that paratasitize bacteria
c. A virus that eats other viruses
d. A bacteria that kills viruses

9. The first virus ever found was:
a. Tetanus
b. E. boli
c. E. coli
d. Tobacco Mosaic

10. There are ______ million viruses in one drop of sea water
a. 10
b. 100
c. 1
d. 15

11. The first vaccination to be developed for inoculation was to help the body develop antibodies against_________________?
a. Rabies
b. Diphtheria, Tetanus and Pertussis
c. Varicella
d. Small pox

12. The nucleic acid of a virus is:
a. DNA only
b. RNA only
c. Both DNA and RNA
d. Either DNA or RNA

14. Because this virus injected it's DNA into our DNA when we were kids we may get shingles as adults.
a. Rabies
b. Polio
c. Chickenpox
d. Impetigo
e. none of the above

15. A fully formed virus that is able to establish an infection in a host is called
a. Viron
b. Prion
c. Capsid
d. Viroid

16. What is the correct order in the life cycle of animal viruses
a. Penetration, adsorption, uncoating, synthesis assembly, release
b. Uncoating, penetration, adsorption, synthesis assembly, release
c. Adsorption, penetration, uncoating, syntheses, assembly, release
d. Syntheses, uncoating, adsorption, penetration, assembly, release

17. The ability of a virus to infect an organism is regulated by
a. The host species.
b. The type of cells.
c. The availability of an attachment site.
d. Cell factors necessary for vital replication.
e. All of the above