Monday, January 19, 2009

Virus-host Interactions

Virus Host Interactions

General Virus Replication Cycle


There are six phases in a virus replication cycle. The six phases are:

  • Attachment
  • Penetration / Entry
  • Uncoating
  • Replication and Expression
  • Assembly
  • Release

Virus Life Cycle – Growth Curve




In the attachment part, virus attached to the host cell receptor and gain entry into the cell. In the eclipse stage, virus is busy with replication. Virus titre decreases when there are no infectious particles present during replication process. Virus is detected in external medium only when released. In the burst or released part, new progeny virus gathered and is then released.

Attachment and Entry
Virus attachment protein (VAP) attaches to the receptor of the host cell. Receptor on the host cell enable virus to gain entry into the host cell. Virus can enter the host cells through three different routes. The three different routes are:
  • Direct penetration
  • Fusion (direct penetration)
  • Endocytosis

Receptors on Host Cells
The cells surface molecule contains glycoprotein and glycolipid. Glycoprotein will have sugar group attached to the protein, and glycolipid will have fat or lipid group attached to it. There are many receptors for many different viruses. These receptors have different functions. Viruses take immediate advantage to use these receptors for attachment. Host range and tissue tropism are important factors that must be considered before virus attached to the receptor. Viruses cannot anyhow infect; they must have the right attachment protein. For example, hepatitis head cannot find the attachment protein and thus, heading towards the liver tissue. Human cells do not have particular receptors for virus. Therefore, virus makes use of receptors to attach.

Endocytosis
A process by which materials from outside the cell, such as proteins, are absorbed by cells through engulfing of these materials with their cell membrane is known as endocytosis. All cells of the body use endocytosis due to those important substances are large polar molecules which cannot pass through the plasma membrane.

There are three types of endocytosis. They are:
  • Phagocytosis
  • Receptor-mediated endocytosis
  • Pinocytosis

A process by which cells ingest large objects, such as cells which have undergone apoptosis, bacteria or viruses, is known as phagocytosis. The object is surrounded by membrane, and a large vacuole, phagosome, seal the object.


Receptor-mediated endocytosis is a much more detailed active event in which coated pits are formed when the cytoplasm membrane folds inward. These inward budding vesicles bud to form cytoplasmic vesicles.


Pinocytosis is a process which involved the uptake of solutes and single molecules, such as protein.


Clathrin-mediated endocytosis
Clathrin molecule mediates the major route for endocytosis in most cells. Clathrin is a large protein which helps in the formation of a coated pit on the inner surface of the cell’s plasma membrane. A coated vesicle is formed in the cytoplasm of the cell when this pit buds into the cell. By doing so, a small area of the surface of the cell and a small volume of fluid from outside the cell is brought into the cell.

Infection of Plant and Bacteria


Virus can also be attached to the tool, whereby the tool becomes infected. Tools used on other plants would breach cell wall and then infect the plants. Plant cell wall must be breached before it can be infected. Similarly, infection will only occur in bacteria cell wall when the cell wall is breached. Virus DNA is then infected into the cell.
Stages of life cycle of virus
  • Initiation of infection
  • - Attatchment and entry
  • Replication and expression
    - Genome replication
    - mRNA production, processing and translation
  • Assembly and exit
  • Viral Pathogenesis

Replication and expression
Genome replication and gene expression very closely linked and characteristics of which depends on the nature of the genome.

Classification of virus
Viruses are not usually classified into conventional taxonomic groups but are usually grouped according to such properties as size, the type of nucleic acid they contain, the structure of the capsid and the number of protein subunits in it, host species, and immunological characteristics.

When a new species of known virus family or genus is investigated it can be done in the context of the information that is available for other members of that group. Without classification scheme, each newly discovered virus would be like a black box, everything would have to be discovered and rediscovered. The development of a classification scheme is therefore an important and inevitable consequence. The current classification scheme allows most newly described viruses to be labeled.

We can state with a degree of confidence that most of the major groupings of viruses infecting humans because there are so few virus discoveries now being made which do not fit into the existing classification scheme and domesticated animals have been identified.


The Baltimore Classification
The Baltimore system of virus classification provides a useful guide with regard to the various mechanisms of viral genome replication. The central theme here is that all viruses must generate positive strand mRNAs from their genomes, in order to produce proteins and replicate themselves.

Baltimore Classification of viruses,
based on the method of viral mRNA synthesis
The precise mechanisms whereby this is achieved varies for each virus family. These various types of virus genomes can be broken down into seven fundamentally different groups, which obviously require different basic strategies for their replication. David Baltimore, who originated the scheme, has given his name to the so-called "Baltimore Classification" of virus genomes. By convention the top strand of coding DNA written in the 5' - 3' direction is + sense. Same goes to mRNA sequence. The replication strategy of the virus depends on the nature of its genome. Viruses can be classified into seven (arbitrary) groups:
I: Double-stranded DNA (Adenoviruses; Herpesviruses; Poxviruses, etc)Some replicate in the nucleus e.g adenoviruses using cellular proteins. Poxviruses replicate in the cytoplasm and make their own enzymes for nucleic acid replication.

II: Single-stranded (+)sense DNA (Parvoviruses)Replication occurs in the nucleus, involving the formation of a (-)sense strand, which serves as a template for (+)strand RNA and DNA synthesis.

III: Double-stranded RNA (Reoviruses; Birnaviruses)These viruses have segmented genomes. Each genome segment is transcribed separately to produce monocistronic mRNAs.

IV: Single-stranded (+)sense RNA (Picornaviruses; Togaviruses, etc)a) Polycistronic mRNA e.g. Picornaviruses; Hepatitis A. Genome RNA = mRNA. Means naked RNA is infectious, no virion particle associated polymerase. Translation results in the formation of a polyprotein product, which is subsequently cleaved to form the mature proteins.b) Complex Transcription e.g. Togaviruses. Two or more rounds of translation are necessary to produce the genomic RNA.

V: Single-stranded (-)sense RNA (Orthomyxoviruses, Rhabdoviruses, etc)Must have a virion particle RNA directed RNA polymerase.a) Segmented e.g. Orthomyxoviruses. First step in replication is transcription of the (-)sense RNA genome by the virion RNA-dependent RNA polymerase to produce monocistronic mRNAs, which also serve as the template for genome replication.b) Non-segmented e.g. Rhabdoviruses. Replication occurs as above and monocistronic mRNAs are produced.

VI: Single-stranded (+)sense RNA with DNA intermediate in life-cycle (Retroviruses)Genome is (+)sense but unique among viruses in that it is DIPLOID, and does not serve as mRNA, but as a template for reverse transcription.

VII: Double-stranded DNA with RNA intermediate (Hepadnaviruses)This group of viruses also relies on reverse transcription, but unlike the Retroviruses, this occurs inside the virus particle on maturation. On infection of a new cell, the first event to occur is repair of the gapped genome, followed by transcription.

Replication of Hepititis B virus
hepatitis B virus (HBV) replication by noncytolytic mechanisms that either destabilize pregenomic (pg)RNA-containing capsids or prevent their assembly. Using immortalized murine hepatocyte cell lines stably transfected with a doxycycline (dox)-inducible HBV replication system, we now show that replication-competent pgRNA-containing capsids are not produced when the cells are pretreated with IFN-β before HBV expression is induced with dox. Furthermore, the turnover rate of preformed HBV RNA-containing capsids is not changed in the presence of IFN-β or IFN-γ under conditions in which further pgRNA synthesis is inhibited by dox removal. In summary, these results demonstrate that types 1 and 2 IFN activate hepatocellular mechanism(s) that prevent the formation of replication-competent HBV capsids and, thereby, inhibit HBV replication.

Virus genome of Hepatitis B
It is circular, and partially doubled-stranded DNA with 4 open reading frames, namely the HBsAg (pre-S1, pre-S2 and S), HBcAg (pre-core and core), polymerase (multifunctional), and HBxAg (transactivating factor). It replicates largely in the liver through RNA intermediate and reverse transcription.

The genes of Hepatitis B virus (HBV).
Thick black lines represent two DNA strands, thin lines indicate locations of genes. The DNA of HBV is a rare example that its two strands do not have the same length.
Diagrammatic representation of the HBV genome. The inner circle represents the virion genomic DNA that is packaged within viral particles in the cytoplasm of infected cells, and the dashes indicate the region of the genome which is incompletely synthesized. The thick arrows represent open reading frames corresponding to core, envelope (surface antigen), polymerase (pol), and HBx proteins. The thin lines represent HBV RNAs.

Regulation and expression
The expression of hepatitis B virus (HBV) genes is regulated by a number of transcription factors. One such factor, Sp1, has two binding sites in the core promoter and one in its upstream regulatory element, which is also known as the ENII enhancer. In this study, we have analyzed the effects of these three Sp1 binding sites on the expression of HBV genes. Our results indicate that both Sp1 binding sites in the core promoter are important for the transcription of the core RNA and the precore RNA. Moreover, while the downstream Sp1 site (the Sp1-1 site) in the core promoter did not affect the transcription of the S gene and the X gene, the upstream Sp1 site (the Sp1-2 site) in the core promoter was found to negatively regulate the transcription of the S gene and the X gene, as removal of the latter led to enhancement of transcription of these two genes. The Sp1 binding site in the ENII enhancer (the Sp1-3 site) positively regulates the expression of all of the HBV genes, as its removal by mutation suppressed the expression of all of the HBV genes. However, the suppressive effect of the Sp1-3 site mutation on the expression of the S gene and the X gene was abolished if the two Sp1 sites in the core promoter were also mutated. These results indicate that Sp1 can serve both as a positive regulator and as a negative regulator for the expression of HBV genes. This dual activity may be important for the differential regulation of HBV gene expression.

Translation of protein
Amino acids are the monomers which are polymerized to produce proteins. Amino acid synthesis is the set of biochemical processes (metabolic pathways) which build the amino acids from carbon sources like glucose. Not all amino acids may be synthesised by every organism, for example adult humans have to obtain 8 of the 20 amino acids from their diet.
Assembly and exit
Different types of virus have varying sites of synthesis and replication. For example, synthesis and replication for DNA viruses occur in the cell’s nucleus while it is usually the cytoplasm for RNA viruses. Virus assembly depends on the site of synthesis and such sites are the nucleus, endoplasmic reticulum and the Golgi apparatus aka Golgi body. Aside from this, assembly also occurs in the viroplasm which is an inclusion body in a cell.
When the virus has replicated and multiplied, they would want to leave the infected cell and infect other cells. However, they require an envelope to enclose the DNA as well as to bind with the other healthy cells so that they can infect. The viral envelope is the typical lipid bilayer, derived from the host cell itself and sources usually come from the nuclear membrane, endoplasmic reticulum, Golgi apparatus/body and plasma membrane. It also depends on where the virus ‘bud’ off from the host.
Budding is a method which viruses use to exit the cell.



It is an example of asexual reproduction because the buddings are genetically identical.
Other methods for exit would be cell lysis. This method releases the virus from the infected cell by bursting its membrane and this kills the cell as well. Another method is by accumulation of virus particles in vesicles and released via exocytosis. Exocytosis is the process where vesicles containing the virus is secreted/excreted out of the infected cell.

An example of a virus that spreads by budding is the Sindbis virus.

Viral Pathogenesis
There are a variety of ways that viruses can enter the host.
1. Skin
- Abrasions and cuts.
2. Eyes
- Conjunctiva. The conjunctiva helps in preventing microbes from entering the eye as well as physical harm. So its is highly susceptible to infection.
3. Urogenital tract
- risky sexual behaviours increase the chances for viral entry/infection.


4. Respiratory
- airborne viruses are inhaled.
- different parts of the respiratory system are specific to certain viruses.

5. Alimentary
- infected/contaminated food. E.g. Mad Cow disease.


Virus Spread
Spreading method varies with different viruses. Not only are there different ways of spreading, there are also different types of spreading. There are about 3- 4 types of viral spreads in animals/human hosts and below are 3 types.
1. Systemic infection
- infection of multiple organs or mucosal surfaces.
2. Haematogenous spread
- primary and secondary spread of virus through the bloodstream. In primary spread, the virus infects and replicates in the blood before dissemination to the targeted organs. However, in secondary spread, the virus infects and replicates elsewhere (usually on mucosal membranes) before dissemination via the bloodstream to the targeted organs.
3. Neural spread
- infection of the nervous system which includes the central nervous system(CNS) and the peripheral nervous system(PNS). Infection occurs more specifically in the inner areas of the nerves as seen in the second picture. Different virus also affect the different areas of the nerves. An example of neural infection by viruses are measles – cause inflammation of the brain. Enteroviruses are the leading causes for neural spread.


Virus Transmission/Shedding
This is important in the survival/propagation of the virus. The virus needs to be spread so that it can continue reproducing and ensuring the survival of the virus species. The effectiveness of viral transmission depends on the virus concentration and the route of transmission. The higher the viral concentration, the higher the chances of transmission. Some modes of virus transmission include respiratory secretions and salivary pathways.
There are a few different ways/modes of viral transmission.
1. Blood
There are a few ways that the virus can infect the blood and one way is by arthropods. They transmit arthropod-borne viruses (arbovirus) such as flaviviruses and togoviruses upon biting and the virus enters the blood which may cause viraemia.
Another way of blood infection would be via direct blood/bodily fluid contact or exposure infected items or people. Some of such viruses include the Hepatitis strain and well as the Human Immunodeficiency Virus (HIV).
2. Saliva
The most common way for transmission is via kissing. Sharing of utensil may also promote virus transmission as there is saliva involved. Examples of such viruses are the herpes viruses and retroviruses.
3. Respiratory secretions
Air-borne viruses and viruses that can only infect the respiratory tract can also be spread by sneezing, coughing, breathing and singing. Although some viruses can be inactivated by drying, it activates again when it enters the body as there is moisture. Contaminated hands from covering a cough or sneeze may also pass on the virus.
4. Feaces
Infection via this method not very common in developed countries where sanitation is relatively good but rather common in areas or poor sanitation, especially third-world countries. Unlike viruses that spread by respiratory means, these viruses are highly resistant to drying meaning they do not get inactivated so easily. This explains allows them to easily infect. Examples of such viruses are the enteric and hepatic viruses.

Virus-induced injury
The cytopathic effect (CPE) (degeneration of the cell due to viral infection) experienced by the cells is on the cellular level. These injuries may include:
  • Detachment from substrate.
  • Membrane permeability. (changes in permeability hinders the transport of materials required for the cell)
  • Lysis. (cell death by bursting its membrane).
  • Shape alteration. (shape of the cell is changed which might affect its functions. E.g. RBC)
  • Apoptosis. (cell death caused by a series of morphological changes that bring about the breakdown of the various functions of the cell).Membrane fusion; syncytium. (a structure containing many nuclei)

Looking at the bigger picture, virus induced injuries can cause some serious damage such as the shutdown of cellular functions in the host. For example, the polio virus shuts down the cellular functions of the neurons in the CNS and PNS (peripheral nervous system), resulting in cell death which leads to paralysis or even death.

Another kind of injury would be immunopathological (immune system/response related). Here, the immune system is impaired due to infection of the immunity cells such as the WBC. The body becomes relatively weak because its own WBCs are fighting each other. However, due to the weakening of the body’s immune system, the body itself will try to enhance its immune response by for example, increasing body temperature to try to kill the virus, thus causing haemorrhagic fevers.

Example of virus infection in the CNS

http://gsbs.utmb.edu/microbook/ch050.htmhttp://www.betterhealth.vic.gov.au/bhcv2/bhcarticles.nsf/pages/Viral_encephalitis?OpenDocument
http://www.medicalook.com/diseases_images/viral-infection1.jpg
http://en.wikipedia.org/wiki/File:Nervous_system_diagram.png
http://en.wikipedia.org/wiki/Alimentary
http://www.infovisual.info/03/065_en.html
http://www.hacompound.com/images/EYEBALL.gif
http://pathmicro.med.sc.edu/mhunt/interferon.htm
http://www.google.com.sg/search?hl=en&q=effect+of+interferon+on+viral+infection&meta
http://pathmicro.med.sc.edu/mayer/vir-host2000.htm
http://www.nlv.ch/Virologytutorials/Classification.htm
http://en.wikipedia.org/wiki/Virus_classification
http://www.fda.gov/ohrms/dockets/ac/02/slides/3885S2_02_Hoofnagle/sld006.htm
http://jvi.asm.org/cgi/content/full/78/23/12725
http://jvi.asm.org/cgi/content/abstract/75/18/8400
http://en.wikipedia.org/wiki/Protein_biosynthesis
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Friday, January 9, 2009

Overview of Microbiology B

History of Viruses

What is poliomyelitis?



Poliomyelitis is a disease caused by infection with the poliovirus. The virus spreads by direct person-to-person contact, by contact with infected mucus or phlegm from the nose or mouth, or by contact with infected faeces.

The virus enters through the mouth and nose, multiplies in the throat and intestinal tract, and then is absorbed and spread through the blood and lymph system. The time from being infected with the virus to developing symptoms of disease (incubation) ranges from 5 - 35 days (average 7 - 14 days).

Risks include:
  • Lack of immunization against polio and then exposure to polio
  • Travel to an area that has experienced a polio outbreak

In areas where there is an outbreak, those most likely to get the disease include children, pregnant women, and the elderly. The disease is more common in the summer and fall.

Between 1840 and the 1950s, polio was a worldwide epidemic. Since the development of polio vaccines, the incidence of the disease has been greatly reduced. Polio has been wiped out in a number of countries. There have been very few cases of polio in the Western hemisphere since the late 1970s. Children in the United States are now routinely vaccinated against the disease.


Outbreaks still occur in the developed world, usually in groups of people who have not been vaccinated. Polio often occurs after someone travels to a region where the disease is common. Thanks to a massive global campaign over the past 20 years, polio exists only in a few countries in Africa and Asia.

What is smallpox?




Smallpox is a contagious, disfiguring and often deadly disease caused by the variola virus. Few other illnesses have had such a profound effect on human health and history. In the 20th century alone, an estimated 300 million people died of smallpox.

The initial signs and symptoms of smallpox, which appear about two weeks after infection, resemble those of the flu — fever, fatigue and headache. Later, severe pus-filled blisters appear on the skin that eventually leave deep, pitted scars. Once symptoms develop, there's no effective treatment for smallpox and no known cure.

Naturally occurring smallpox was finally eradicated worldwide by 1980 — the result of an unprecedented immunization campaign. But the virus didn't disappear entirely. Stocks of smallpox virus, set aside for research purposes, are officially stored in two high-security labs — one in the United States and one in Siberia. This has lead to concerns that smallpox someday may be used as a biological warfare agent.

What is rabies?


Rabies infections in people are rare in the United States. However, worldwide about 50,000 people die from rabies each year, mostly in developing countries where programs for vaccinating dogs against rabies don't exist. But the good news is that problems can be prevented if the exposed person receives treatment before symptoms of the infection develop.

Rabies is a virus that in the U.S. is usually transmitted by a bite from a wild infected animal, such as a bat, raccoon, skunk, or fox. If a bite from a rabid animal goes untreated and an infection develops, it is almost always fatal.

If you suspect that your child has been bitten by a rabid animal, go to the emergency department immediately. Any animal bites — even those that don't involve rabies — can lead to infections and other medical problems. As a precaution, call your doctor any time your child has been bitten.

Who was Edward Jenner?


Edward Jenner was an English country doctor who pioneered vaccination. Jenner's discovery in 1796 that inoculation with cowpox gave immunity to smallpox, was an immense medical breakthrough and has saved countless lives.

Edward Jenner was born on May 17 1749 in the small village of Berkeley in Gloucestershire. From an early age Jenner was a keen observer of nature and after nine years as a surgeon's apprentice he went to St George's Hospital, London to study anatomy and surgery under the prominent surgeon John Hunter. After completing his studies, he returned to Berkeley to set up a medical practice where he stayed until his death in 1823.

What he did?
In 1796 he carried out his now famous experiment on eight-year-old James Phipps. Jenner inserted pus taken from a cowpox pustule and inserted it into an incision on the boy's arm. He was testing his theory, drawn from the folklore of the countryside, that milkmaids who suffered the mild disease of cowpox never contracted smallpox, one of the greatest killers of the period, particularly amongst children. Jenner subsequently proved that having been inoculated with cowpox Phipps was immune to smallpox. He submitted a paper to the Royal Society in 1797 describing his experiment but was told that his ideas were too revolutionary and that he needed more proof. Undaunted, Jenner experimented on several other children, including his own 11-month-old son. In 1798 the results were finally published and Jenner coined the word vaccine from the Latin 'vaccia' for cow.

Who was Louis Pastuer?


Louis Pasteur was a world renowned French chemist and biologist. He was born on December 27 1822 in the town of Dole in Eastern France. Pasteur's parents were peasants; his father was a tanner by trade. He spent the early days of his life in the small town of Arbois where he attended school and where it seems that Pasteur did not do very well, preferring instead to go fishing. His headmaster, however, spotted potential in Pasteur and encouraged him to go to Paris to study. So, aged fifteen Pasteur set off for Paris hoping to study for his entrance exams. Unfortunately, the young Pasteur was so homesick that his father had to travel to Paris to bring him home. He then continued to study locally at Besancon, until he decided to try again in Paris. This time he succeeded and went on to study at the Ecole Normale Superieure. Curiously, although the young Pasteur worked hard during his student days he was not considered to be exceptional in any way at chemistry.

In 1847 Pasteur was awarded his doctorate and then took up a post as assistant to one of his teachers. He spent several years teaching and carrying out research at Dijon and Strasbourg and in 1854 moved to the University of Lille where he became professor of chemistry. Here he continued the work on fermentation he had already started at Strasbourg. By 1857 Pasteur had become world famous and took up a post at the Ecole Normale Superieure in Paris. In 1863 he became dean of the new science faculty at Lille University. While there, he started evening classes for workers. In 1867 a laboratory was established for his discovery of the rabies vaccine, using public funds. It became known as the Pasteur Institute and was headed by Pasteur until his death in 1888.

What he did?
Pasteur founded the science of microbiology and proved that most infectious diseases are caused by micro-organisms. This became known as the "germ theory" of disease. He was the inventor of the process of pasteurisation and also developed vaccines for several diseases including rabies. The discovery of the vaccine for rabies led to the founding of the Pasteur Institute in Paris in 1888.

Who is Robert Koch?


Robert Koch was born in 1843. Koch worked on anthrax and tuberculosis (TB) and he further developed the work of Louis Pasteur. Koch’s fame, alongside that of Alexander Fleming, Edward Jenner, Joseph Lister and Pasteur himself, is firmly cemented in medical history.

What did he discover?
Pasteur was convinced that microbes caused diseases in humans but his work on cholera had failed. He was never able to directly link one microbe with a disease. Koch succeeded in doing this.

The first disease that Koch investigated was anthrax. This was a disease that could seriously affect herds of farm animals and farmers were rightly in fear of it. Other scientists had also been working on anthrax. In 1868, a French scientist called Davaine had proved that a healthy animal that did not have anthrax could get the disease if it was injected with blood containing anthrax. Koch developed this work further and for three years he spent all his spare time finding out what he could about the disease, including its life cycle.

Koch found out that the anthrax microbe produced spores that lived for a long time after an animal had died. He also proved that these spores could then develop into the anthrax germ and could infect other animals.

After this, Koch moved onto germs that specifically affected humans. In 1878, he identified the germ that caused blood poisoning and septicaemia. He also developed new techniques for conducting experiments that influenced the way many other scientists carried out their experiments. He knew that infected blood contained the septicaemia germ but he could not see these germs under a microscope, and therefore, other scientists were unlikely to believe what he thought to be true without the evidence.

Koch discovered that methyl violet dye showed up the septicaemia germ under a microscope by staining it. He also photographed the germs so that people outside of his laboratory could see them.

Koch also devised a method of proving which germ caused an infection. His work was rewarded in 1880 when he was appointed to a post at the Imperial Health Office in Berlin. Here, Koch perfected the technique of growing pure cultures of germs using a mix of potatoes and gelatine. This was a solid enough substance to allow for the germs to be studied better. Koch gathered round him a team of researchers in Berlin in 1881 and began to work on one of the worst diseases of the nineteenth century – tuberculosis (TB).

The TB germ was much smaller than the anthrax germ so the search for it was difficult. Using a more specialised version of his dye technique, Koch and his team searched for the TB germ. In May 1882, Koch announced that his team had found the germ. His announcement caused great excitement. It also generated what became known as ‘microbe hunters’ – a new generation of young scientists who were inspired by the work of both Koch and Pasteur. One of those who was inspired by Koch was Paul Ehrlich.

Koch’s Postulates

  • The organism must be regularly associated with the disease and its characteristic lesions.
  • The organism must be isolated from the diseased hosts and grown in culture.
  • The disease must be reproduced when a pure culture of the organism is introduced into a healthy susceptible host.
  • The same organism must again be re-isolated from the experimentally infected host.
Discovery of Viruses


On 12th February 1892, Dmitri Iwanowski, a Russian botanist, presented a paper to the St. Petersburg Academy of Science which showed that extracts from diseased tobacco plants could transmit disease to other plants after passage through ceramic filters fine enough to retain the smallest known bacteria. This is generally recognised as the beginning of Virology. Unfortunately, Iwanowski did not recognize that he had discovered a new type of infectious agent.


Six years later, in 1898, a Dutch scientist, Martinus Beijerinick confirmed & extended Iwanowski's results on tobacco mosaic virus & was the first to develop the modern idea of the virus, which he referred to as contagium vivum fluidum ('soluble living germ'). He discovered that the infectious agent which passed through the filter could reproduce but would not grow on Petri dishes used to cultivate bacteria. He further realized that these agents required the presence of a host cell to reproduce. He named the agent responsible for tobacco mosaic disease a virus, after the Latin term for poison. He thought that this agent must be much smaller and simpler than bacteria. The subsequent crystallization and electron microscope images obtained by the American scientist, Wendell Stanley, in 1935 confirmed this, and the agent was named tobacco mosaic virus.



Tobacco mosaic virus causes stunted plant growth and mottled, discoloured plant leaves, especially in tobacco and other members of the tomato family (Solanceae).

In 1898, Freidrich Loeffler & Paul Frosch showed that a similar agent was responsible for foot-and-mouth disease in cattle. Thus these new agents caused disease in animals as well as plants. In spite of these findings, there was resistance to the idea that these mysterious agents might have anything to do with human diseases.

References
http://kidshealth.org/parent/infections/bacterial_viral/rabies.html
http://www.mayoclinic.com/health/smallpox/DS00424
http://www.zephyrus.co.uk/louispasteur.html
http://www.zephyrus.co.uk/edwardjenner.html
http://www.bioedonline.org/slides/slide01.cfm?q=dimitri+ivanowsky&dpg=1
http://www.historylearningsite.co.uk/robert_koch.htm
http://www.umm.edu/ency/article/001402.htm
www.raw-milk-facts.com/tuberculosis.html
library.thinkquest.org/26644/us/pasteur.htm
http://www.bbc.co.uk/
http://www.microbiologybytes.com/introduction/introduction.html
http://sg.wrs.yahoo.com/_ylt=A0S0zu11c2NJNV4ABlUu4gt./SIG=12ic5snmm/EXP=1231340789/**http%3A/www.cbe21.com/subject/biology/photo.php%3Fphoto_id=1343
www.inra.fr/hyp3/pathogene/3tomovi.htm
http://www.medizin.uni-greifswald.de/mikrobio/forschung/virologie.html
http://www.nlm.nih.gov/
www.news.bbc.co.uk
http://www.who.int/
www.encarta.msn.com
www.viewzone.com/smallpox.html

Nature of Viruses

Viruses are:

  • Sub-microscopic, obligate intracellular parasites.
  • Viruses are not made up of cells. Compared to animal and plant cells, viruses are structurally simple. Viruses are even simpler than bacteria cells. The basic of structure of all viruses is similar. Viruses have a core of nucleic acid surrounded by a protein coat. At their core, all viruses contain either DNA or RNA.
  • They are so simple that they are technically not even considered "alive." There are six characteristics of all living things:
    - Adaptation to the environment
    - Cellular makeup
    - Metabolic processes that obtain and use energy
    - Movement response to the environment
    - Growth and development
    - Reproduction
  • A virus is not able to metabolize, grow, or reproduce on its own, but must take over a host cell that provides these functions; therefore a virus is not considered "living." The structure of a virus is extremely simple and is not sufficient for an independent life.
  • Viruses are structurally simpler than regular cells. Outside of the host cells, viruses are inactive. However, inside living cells, viruses show some of the characteristics of living things.
    Virus particles are produced from the assembly of pre-formed components, whereas other agents 'grow' from an increase in the integrated sum of their components & reproduce by division.
  • Virus particles (virions) themselves do not 'grow' or undergo division.Viruses lack the genetic information which encodes apparatus necessary for the generation of metabolic energy or for protein synthesis (ribosomes).

General Properties of Viruses
  • Obligate parasites
  • Sub-cellular size
    - Viruses are among the smallest infectious agents, and most of them can only be seen by electron microscopy and not light microscope. Their sizes range from 20 to 300 nm. They are so small that it would take 30,000 to 750,000 of them, side by side, to stretch to one cm.
  • Structurally simple
    1. Nucleic acid - contains 3-400 genes
    Deoxyribonucleic Acid (DNA) -unique features
    - Single and/or double stranded
    - Glycosylated and/or methylated
    - Gaps present in double stranded molecule
    - Circular or linear
    - Bound protein molecules
    - Unique purine and/or pyrimidine bases present
    - Ribonucleotides present
    Ribonucleic Acid (RNA) - Unique features
    - Single or double stranded
    - Segmented or unsegmented
    - Bound protein molecules
    - Unique purine and/or pyrimidine bases present
    - Folding pattern
    2. Capsid - The capsid accounts for most of the virion mass. It is the protein coat of the virus. It is a complex and highly organized entity which gives form to the virus. Subunits called protomeres aggregate to form capsomeres which in turn aggregate to form the capsid.
    3. Envelope - this is an amorphous structure composed of lipid, protein and carbohydrate which lies to the outside of the capsid. It contains a mosaic of antigens from the host and the virus. A naked virus is one without an envelope.
    4. Spikes- These are glycoprotein projections which have enzymatic and/or adsorption and/or hemagglutinating activity. They arise from the envelope and are highly antigenic.

  • Wide variety of host


Structure of viruses

Each virus is made up of two elementary components. The first is a strand of genetic material, either deoxyribonucleic acid (DNA) or ribonucleic acid (RNA). Unlike living cells, viruses will have either DNA or RNA, but not both. The genetic material is a blueprint for determining the structure and behavior of a cell. In a virus, a protein coat called a "capsid" surrounds the nucleic acid. This coat serves to protect the nucleic acid and aid in its transmission between host cells. The capsid is made of many small protein particles called "capsomeres," and can be formed in three general shapes – helical, icosahedral (a 20-sided figure with equilateral triangles on each side), and complex. Some of the more advanced viruses have a third structure that surrounds the capsid. This is called the "envelope" and is composed of a bilipid layer, like the membrane on a cell, and glycoproteins, which are protein and carbohydrate compounds. The envelope serves to disguise the virus to look like a 'real' cell, protecting it from appearing as a foreign substance to the immune system of the host. The structure of a virus is closely related to its mode of reproduction.

Reproduction
A virus's sole purpose is to reproduce, but it needs a host cell to do so. Once a suitable host cell has been located, the virus attaches to the surface of the cell or is ingested into the cell by a process called "phagocytosis." It then releases its genetic material into the cell, and essentially shuts down normal cell processes. The cell stops producing the proteins that it usually makes and uses the new blueprint provided by the virus to begin making viral proteins. The virus uses the cell's energy and materials to produce the nucleic acid and capsomeres to make numerous copies of the original virus. Once these 'clones' are assembled, the virus causes the host cell to rupture, releasing the viruses to infect neighbouring cells.


Reference
http://www.microbiologybytes.com/introduction/introduction.html
http://www.kcom.edu/faculty/chamberlain/Website/Lects/PROPERT.HTM
http://www.miamisci.org/youth/unity/Unity1/Lubens/pages/characteristic.html
http://en.wikipedia.org/wiki/Viruses
http://www.roshanpakistan.com/
http://www.pinkmonkey.com/studyguides/subjects/biology-edited/chap14/b1400001.asp
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Classification of Viruses

Taxonomy and Classification of Viruses

Introduction
There are numerous types of virus present and new species are still being discovered today. They are present in almost every type or organism such as animals, plants, bacteria and fungi and thus require a system of classification so as to have a better understanding on the type of viruses present. According to the WHO, FAO and other international agencies, there are approximately 30,000 viruses, strains and subtypes but many still remain unassigned because they are not properly categorized.

An example of taxonomy of organisms



The first International Congress of Microbiology was held in Paris in 1930 but it was only during the International Congress of Microbiology held in Moscow in 1966, that the first attempt to come up with a system of classification of viruses was made.

The international Committee on Taxonomy of Viruses (ICTV) is a committee that handles the taxonomy of viruses. They have come up with a universal taxonomic scheme that follows the hierarchy taxa: Order - Family – Sub-family – Genus – Species. So far they have approved of 3 orders, 73 families, 9 subfamilies, 287 genera and 5450 viruses from 1950 species.Their first report was submitted in 1971 and the subsequent reports where released in 1976, 1979, 1982, 1991, 1995, 2000 and 2005.

There is also a classification criteria
  • Nature of genome and sequence relatedness.
  • Virus structure (symmetry, shape, etc).
  • Natural host range.
  • Cell and tissue tropism.
  • Pathogenicity and cytopathology.
  • Mode of transmission.
  • Physiochemical properties of virions.
  • Antigenic properties of viral proteins.

Despite having the ICTV, there are other people who come up with their own methods of classification for viruses. Two such examples would be Lwoff’s scheme of classification and David Baltimore’s system for classification. Lwoff’s scheme is based on several factors. They are shared properties of viruses instead of host properties, the physical properties of virus, nucleic acid of virus, symmetry of capsid, presence/absence of an envelope and the dimensions of virion and capsid. Baltimore’s system however, is solely based on the viral genome and its relationship to mRNA.

Baltimore’s system of classification separates the several kinds of DNA and RNA into seven classes as different viruses have different types DNA and RNA. Thus under this system of classification, the viruses are grouped according to their type of DNA and RNA. Below is a table of the classes.


dsDNA - double-stranded DNA.
ssDNA - single-stranded DNA
dsRNA - double-stranded RNA
(+) sense - positive(+) sense
(-) sense - negative(-) sense
(+) sense RNA is identical to mRNA while (-) sense RNA is complimentary to mRNA.
RNA reverse transcribing virus is transcribed from RNA to DNA.
DNA reverse transcribing virus is a DNA polymerase enzyme transcribed from ssRNA to DNA.



An example of classification



Reference
http://en.wikipedia.org/wiki/International_Committee_on_Taxonomy_of_Viruses
http://www.iums.org/Congresses/index.html)-17/12/08
http://www.ictvonline.org/virusTaxInfo.asp)-17/12/08
http://biology.about.com/od/evolution/a/aa092304a.htm)-17/12/08
http://en.wikipedia.org/wiki/Baltimore_classification
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