Viruses

About a century ago at the time of Louis Pasteur (1822-1895) and Robert Koch (1843-1910), the word “virus” was  generally referred to as a poison associated with disease and death. The present notion of virus is entirely different. Now viruses are recognized as particles of nucleic acid often with a protein coat. They replicate in living cells and cause many diseases such as influenza, hepatitis, small pox and AIDS. In this section the focus is on the properties of viruses and life cycle of bacterial viruses, also known as bacteriophages. Some diseases caused by viruses shall also be discussed in this section. The branch which deals with the study of viruses is known as virology.

The word virus is derived from Latin word venome meaning poisonous fluid. It can be defined as non cellular infectious entities which contain either RNA or DNA, normally encased in proteinaceous coat, and reproduce only in living cells. Viruses utilize the biosynthetic machinery of the host for its own synthesis and then transfer themselves efficiently to other Cell.

Some viral diseases have been known for centuries. In fact, the first infectious disease against which effective method of prevention was developed was a viral disease. In 1796, Edward Jenner first vaccinated an 8 years old boy with material removed from cowpox lesion on the hand of milkmaid. After six weeks the boy was inoculated with pus from a small pox victim, but he did not develop the disease. Later Jenner used material for vaccination from cowpox lesions and successfully vaccinated 23 persons. As the material he used was obtained from cow (latin vacca), latter the term vaccination was used by Louis Pasteur for inoculation against disease.

In 1884, one of Pasteur’s associates, Charles Chamberland, found that bacteria can not pass through porcelain filters, while agent responsible for rabies (a disease which is transferred to human by bites of rabid dogs, foxes, cats, bats and other animals) can pass through these filters. As in those days the word virus was loosely used to describe any toxic substance that caused disease, those unseen filterable agents of disease were described as filterable viruses. In 1892, Ivanowski discovered that the agent which caused tobacco mosaic disease was filterable. He obtained bacteria free filtrate from ground up infected plants and placed it on healthy leaves of tobacco. He observed that filtrate produced the disease in healthy plants. After that, presence of similar filter-passing, ultramicroscopic agents was seen in the victims of many diseses, including foot and mouth disease (1898) and yellow fever (1901).

The filterable agents were first purified in 1935, when Stanley was successful in crystallizing the tobacco mosaic virus. Chemical analysis of these particles showed that they contained only nucleic acid and protein. This suggested that, unlike other forms, viruses are of simple chemical composition.

Characteristics

Viruses are extremely small infectious agents, which can only be seen under an electron microscope. The range in size from 250 nanometer (nm) of poxviruses to the 20 nm of parvoviruses. They are 10 to 1000 times smaller than most bacteria, so they can pass through the pores of filter from which bacteria cannot pass. Viruses cannot be grown on artificial media. They can reproduce only in animal and plant cells or in microorganisms, where they reproduce by replication (a process by which many copies or replicas of virus are formed). Thus the viruses are obligate intracellular parasites.

Viruses lack metabolic machinery for the synthesis of their own nucleic acid and protein. They depend on the host cell to carry out these vital functions. During reproduction in the host cells, viruses may cause disease. All viruses are generally resistant to broad range of available antibiotics such as penicillin, streptomycin and others.

Structure

The complete, mature and infectious particle is known as virion. The virions are composed of a central core of nucleic acid, either DNA or RNA, which is also known as the genome and is surrounded by a protein coat, the capsid. Capsid gives definite shape to virion. Capsid is made up of protein subunits known as capsomeres. The number of capsomeres is characteristics of a particular virus. For example 162 capsomeres are present in the capsid of herpes virus and 252 in the capsid of adenovirus which cause some common colds. In some animal viruses the nucleocapsid (nucleic acid and capsid) is covered by another membrance derived from the host cell, the envelope. Non enveloped viruses are known as naked virions. Animals and plant viruses may be polyhedron (having many sides), helical (spiral), enveloped or complex.

Bacterio-phages occur in two structural forms having cubical or helical symmetry. In general appearance cubical phages are regular solid or icosahedral (having 20 faces), and helical phages are rod shaped. Many phages consist of head and tail. In those cases heads are polyhedral but tails are rod shaped. Morphology of some viruses and bacteriophages has been shown in fig 5.3.

Life Cycle Of Bacteriopages

Earlier researches on bacteriphages were mainly on limited number of phages that infect Escherichia coli. Of these the best known phages are T phages (T for type).

Among T phages, the T2 and T4 phages are mainly used in phage studies. The overall structure of T4, studied with electron microscopy, resembles that of tadpole, consisting of head and tail (fig 5.4). the head is an elongated pyramidal (having two triangular structures with common base), hexagonal, prism – shaped structure, to which straight tail is attached. Within the head double stranded DNA molecule is present. The structure of phage tail is more complex than head. A layer of distinct protein forms the inner tube of core, which is enclosed in sheath made up of another type of protein. On one side of sheath is collar and on other side is end plate. To end plate six tail fibers are attached, which are the structures for attachment. The volume of the phage is about 1/1000 of the host.

The bacteriophage replicates only inside the bacterial cell. The first step in the replication of a bacteriophage is its attachment (adsorption) to host cell at receptor site on the cell wall of bacterium. During attachment, week chemical union between virion and receptor site takes place. In the next step, Penetration, the tail releases the enzyme lysozyme to dissolve a portion of the bacterial cell wall. The tail sheath contracts and tail core is forced into the cell through cell wall and cell membrane. The virus injects its DNA into the cell just as the syringe is used to inject the vaccine. The protein coat, which forms the phage head and tail structure of virus remains outside the cell (fig 5.5). many animal viruses, however enter the host cell as a whole.

Immediately after entering the host cell, the viral nucleic acid takes the control of the host’s biosynthetic  machinery and induces the host cell to synthesize necessary viral components (DNA, proteins), and starts multiplying. About 25 minutes after initial infection, approximately 200 new bacteriophages are formed, bacterial cell bursts, i.e., it undergoes lysis. Newly formed phages are released to infect the bacterial and another cycle, the lytic cycle begins (fig. 5.6). the phage which causes lysis of the host cell is known as lytic or virulent phage.

All infections of bacterial cells by phages do not result in lysis. In some cases viral DNA, instead of taking over the control of host’s machinery, becomes incorporated into the bacterial chromosome. Phage in this state is called prophage and this process is known as lysogeny.

In this condition the bacterium continues to live and reproduce normally. Viral DNA being the part of bacterial chromosome passes to each daughter cell in all successive generations. Some times, however, the viral DNA gets detached from the host’s chromosome and lytic cycle starts. This process is called induction. Lysogenic bacteria are resistant to infection by the same or related phages. The phage which causes lysogeny is called temperate (lysogenic) phage.

Fig. 5.6 Replication of a bacteriophage. After adsorption and penetration, the virus DNA undergoes prophage formation (1) In the lysogenic cycle, phages can exist harmlessly as a prophage with in the host cell for long perods of time. Each time the bacterial chromosome is replicated, the prophage also is replicated, and hence all daughter bacterial cell are “infected” with the prophage. Induction involves either a spontaneous or environmentally induced excision of the prophage from the bacterial chromosome. (2) A typical lytic cycle, involves synthesis and maturation synthesis and maturation of phage and new phages are released.

Classification Of Viruses

Virus morphology and nucleic acid properties are most important for classifying plant, animal and bacterial viruses. The genetic material may be DNA or RNA naked, enveloped or complex. On the basis of morphology viruses are classified into rod shaped (T M V), spherical (poliovirus) and tadpole like bacteriophage viruses etc. fig 5.3 and 5.4

Some Viral Diseases

There are many diseases which are caused by viruses. Only those are being mentioned here which are common in Pakistan.

Small pox: smallpox, which is caused by pox viruses (the DNA enveloped virus) is an ancient disease that is known to have occurred as epidemic in china as early as the twelfth century B.C. until the early twentieth century, small pox was a common disease throughout the world. In small pox, raised fluid-filled vesicles are formed on the body which become pustules later on and form pitted scars, the pocks. By 1950’s immunization and other control measures had largely decreased the danger, but it is still present In the third world countries where many people are affected.

Herpes simplex: herpes virus (DNA virus) is responsible for this disease. It is naturally occurring disease of mankind. In this vascular lesions in the epithelial layers of ectodermal tissues are formed. Most commonly this disease occurs in the mouth, on the lips, and at other skin sites.

Influenza: influenza viruses are enveloped RNA viruses. Influenza is wide spread disease in man and occurs in epidemic form.

Mumps and measles: mumps and measles viruses belong to group Paramyxoviruses. They are large, enveloped, RNA viruses. Mumps is highly contagious, wide spread, but seldom fatal. About 60% of adults are immune to it. Measles is one of the commonest diseases of the childhood and adult human population is equally susceptible the world over. This disease develops immunity in its victim.

Polio: poliomyelitis, caused by polio virus, is found all over the world. It occurs mostly in childhood. The age at which primary infection occurs varies with social and economic factors. The polioviruses are the smallest known viruses land contain RNA in spherical capsid. Some common human viral dieases are shown in Fig 5.7

Fig. 5.7: Some common human viral diseases

Retroviruses

RNA tumor viruses have been known for many years. These viruses are widely distributed in nature and are associated with tumor production in a number of animal species, such as fowl, rodents and cats. The most familiar of viruses is the human immunodeficiency virus (HIV) which causes acquired immune deficiency syndrome (AIDS)

The single stranded RNA tumor viruses, which also include retroviruses (oncoviruses), are spherical in form, about 100nm in diameter and enveloped by host plasma membrane, although a few retroviruses are non specific that is they can infect any cell, most of them can infect only host cells that possess required receptors. In the case of AIDS virus, the host cell possesses a receptor that allows the viral adsorption and penetration in several types of leukocytes (white blood cells) and tissue cells. The retroviruses have a special enzyme called reverse transcriptase, which can convert a single stranded RNA genome into double stranded viral DNA. Not only this DNA can infect host cells, but it also can be incorporated into host genome as a provirus that can be passed on to progeny cells. In this way some of retroviruses can convert normal cells into cancer cells.

Acquired Immune Deficiency Syndrome (AIDS)

The AIDS was reported by some physicians in early 1980’s in young males having one or more of complex symptoms such as severe pneumonia, a rare vascular cancer, sudden weight loss, swollen lymph nodes and general loss of immune functions. All these young patients were homosexuals. Soon after the disease was discovered in nonhomosexual patients who  were given blood (blood transfusion) or blood products. In 1984 the agent causing the disease was identified b research teams from Pasteur institute in France and national institute of health in USA. In 1986 the virus was named as human immunodeficiency virus (HIV) (Fig 5.8). the major cell infected by HIV is the helper T-lymphocyte, which is major component of immune system. As the HIV is the infection continues in the host, the decrease of helper T-lymphocytes results in failure of the immune system and the infected person becomes susceptible to other diseases. Cells in central nervous system can also be infected by HIV Fig 5.9 recent studies on HIV reveal that the virus infects and multiplies in monkey but does not cause disease in them, which means that HIV is host specific.

Fig. 5.8 Human immunodeficiency virus (HIV)

The HIV is transmitted by intimate sexual contact, contact with blood and breast feeding. Healthcare workers can also acquire HIV during professional activities. Avoiding the direct contact with HIV is important measure for preventing the disease. Prevention of intravenous drugs with common syringes and use of sterile needles/ syringes and utensils is important. Now vaccine against HIV has been synthesized and its experimental administration in humans started in early 2001 in south Africa.

Fig 5.9 Infection cycle of HIV

Hepatitis

Hepatitis is an inflammation of the liver. It is usually caused by viral infection, toxic agents or drugs. It is characterized by jaundice, abdominal pain, liver enlargement, fatigue and some times fever. It may be mild or can be acute and can lead to liver cancer. The different types of viral hepatitis are Hepatitis A (formerly called infectious hepatitis is transmitted by contact with faeces from infected individuals). Hepatitis B (serum hepatitis). Hepatitis C (formerly called non-A, non-B hepatitis) passes through blood, from mother to child during pregnancy and afterward and by sexual contact. Hepatitis D (delta hepatitis), Hepatitis E (a virus transmitted through the faeces of an infected person), Hepatitis F, G (caused by viruses yet unidentified). Viruses of hepatitis A, B and C are better known. Hepatitis A virus (HAV) is an RNA virus (non enveloped), which causes mild short term, less virulent disease. Hepatitis C virus (HCV) is also RNA virus (enveloped) causes infusion hepatitis, which is less severe than hepatitis A or hepatitis B, but hepatitis C often leads to chronic liver disease. Most recent work of Halbur and coworker (2001) reveals that pig could be the source of infection of hepatitis E.

Hepatitis B (HBV) is the second major form of hepatitis. It is caused by DNA Virus which is very common in Asia, china, Philippines, Africa and the Middle East. Hepatitis B is transmitted by the exchange of body fluids, for example blood serum, breast milk and saliva, from mother to child during birth of afterward and by sexual contact… during acute attacks of Hepatitis B fatigue, loss of appetite and jaundice are reported. Infected persons can recover completely and become immune to the virus. People with chronic hepatitis infection are at the risk of liver damage. Hepatitis can be controlled by adopting hygienic measures, with routine vaccination and screening of blood/ organ/ tissue of the donor.

Not: genetically engineered vaccine is available for HBV. Vaccine is also available for HAV but not for HCV.