Natural Defenses against Viral Infections:

1. Interferons (Isaacs and Lindenmann, 1957). Interferons are antiviral proteins (a class of glycoproteins) which diffuse out from infected cells, enter into the cells in the neighbourhood and impart a defense mechanism to these cells against viral infections by inhibiting the synthesis of viral proteins. These are therefore used for therapeutic and preventive purposes in viral infections, interferons are always secreted by host cells against viral infection.

2. Body Immunity. Viruses are good antigens to induce active production of specific antibodies (by lymphocytes).

3. Immunoprophylaxis – Vaccines: Vaccines contain inactivated (attenuated) virions, which cannot cause the concerned diseases, but still act as antigens to induce antibody production by the immune system of the body.

4. Chemotherapy – Antiviral Drugs: The chemotherapeutic agents antibiotics which are used in the treatment and control of bacterial diseases are ineffective for viral diseases. However, some antiviral drugs have been prepared. These include (i) Thiosemicarbozone (for treatment and prevention of smallpox), (ii) Ribavirin or Virozole (for influenza),
(iii) Deoxyuridines, Acylovir (for herpes), (iv) Foscarnet (for hepatitis-B) etc.

2g) Viruses: Study of Bacteriophages

1. Discovery of bacteriophages is associated with Twort when he reported viral disease in bacteria. The term bacteriophages was coined by De Herelle. They are viruses, which attack bacteria. A typical bacteriophage looks like a tadpole/sperm comprising a hexagonal head of protein and a tail also a protein they show binal symmetry. Head is 1000A long and 650A in width; length of the tail is 1000A. Thus, head and tail are equal in length. Infective part of the bacteriophage in most of the cases is ds-linear DNA and it is present in hexagonal head. Joint of head and tails is neck, which is covered by collar of protein. Tail ends in end plate that develops 3 pairs of tail fibers of protein. Bacteriophages that attack E.coli are called coliphage or T-phages. They were numbered as T₁, T₂, T₃, T₄, T₅, T₆, T₇ etc by Delburck, T₂, T₄, T₆ etc are T-even phages T₁, T₃, T₅, etc or T-odd phages.
2. A bacteriophage comes into contact with the bacterial (host) cell through tail fibres. A passage is created in the host cell once the mucocomplex cell wall of bacteria is broken by lysozyme of bacteriophage. Once the passage is created, ds-linear DNA of bacteriophage is dropped inside the host cell. Empty protein coat i.e. Ghost protein remains out the host cell and disappears later on. Infective part or genetic material in ÆX174 phages is ss circular DNA and it is RNA in MS-2 & R17 phages.
3. Phage DNA dropped inside host cell may be virulent or temperate. Bacterial cell is destroyed if phage DNA is virulent, bacterial cell is not destroyed is phage DNA is temperate.
4. Destruction of bacterial cell by virulent phage DNA is called lysis. The sequence of events leading to lysis of bacterial cell are:
   • Virulent phage DNA dropped inside bacterial cell.
   • Multiplication of phage DNA inside host cell i.e. Formation of prophage. Formation of complete phages. (End of latent period or period of eclipse of phages).
   • Destruction or lysis of bacterial cell (Total time: 15-20 minutes).*
5. A bacterial cell is not destroyed if phage DNA is temperate. Temperate phage DNA is attached with host DNA; this is called lysogeny. A lysogenic bacterial cell behaves normally till temperate phage DNA is attached. Lysogeny in bacteria was first reported by Lwoff. Lwoff also coined the term l-phage for those phages in which tail terminates into single tail fibre.
   • Lysogeny may be of 3 types. They are l-phage lysogeny; P₁-phage lysogeny and mu-phage lysogeny. In l-phage lysogeny, temperate phage DNA is attached with bacterial DNA at specific place i.e. at 'gal' & 'bio' genes of bacterial DNA. In P₁-phage lysogeny, temperate phage DNA is attached with any place other than gal's genes. In mu-phage lysogeny, temperate phage DNA is never attached with bacterial DNA, remain in bacterial cytoplasm as plasmid.
   • A lysogenic bacterial cell shows different behaviour when exposed to different dosages of UV rays:

MICROBIOLOGY: STUDY OF VIRUSES

2a) Viruses: Introduction

1. Study of viruses is called virology and Beijerinck is recognized as 'father of virology'. He reported enormous power of multiplication of viruses inside host cell. He also studied mechanism of nitrogen fixation by microorganisms like bacteria.
2. The term 'virus' has been derived from Greek word 'virion' which means 'poison'. Viruses are defined as hyperparasites and 'filterable entities' not having any cellular organization and defined as hyperparasites and 'filterable entities' not having any cellular organization and because of this cell theory is not applicable on them. They are thus exceptions to cell theory. They form crystals when taken out of the host cell. This shows non-living nature of viruses, which was first revealed by Stanley while working on 'Tobacco Mosaic Virus'. Nucleoprotein structure of viruses was first studied by Bawden & Pierre. In nucleoprotein structure of viruses, core of nucleic acid is surrounded by coat of protein. Viruses are unique as they contain only one type of nucleic acid. Mutation in viruses was first reported by Delbruck. Mutation and enormous power of reproduction confirm living nature of viruses. Viruses are thus the only entities, which have characters of non-living and living entities both. They are thus 'connecting links' between non-living entities and lining entities.

2b) Viruses: Historical Studies

Studies in viruses started with independent works of Pasteur and Adolf Mayer. Pasteur prepared vaccines of rabies virus and used the term 'virus' for first time. Mayer reported mosaic like spots on leaves of tobacco plant infected with virus. He described the virus as Tobacco Mosaic Virus [TMV]. Ivanowski passed the cell sap of infected tobacco leaves through bacteria proof bacteria proof filter and sprayed the filtrate on healthy leaves. Mosaic spots appeared again. Ivanowski through his experiment described viruses as filterable entities. Famous conclusion of Beijerinck about viruses i.e. 'contagium vivum fluidum' means sap retains the infection of viruses (living fluid infectant). Takami of Holland studied transmission of viruses through various agencies. He observed that insects are important agencies in transmission of viruses. Insects that transmit viruses are called 'vertors'. Viruses-vector relationship is highly specific.

Culture of viruses was prepared for the first time by Ender. It was poliomyelitis virus. Hershey and Chase observed that nucleic acid is the infective part of virus. They selected Bacteriophages for their experiment. Bacteriophages are DNA containing viruses which attack bacteria. They were discovered by Twort; further studies were made by DeHerelle. Experiment of Hershey & Chase is another example which confirms status of DNA as genetic material. Safferman & Morris discovered 'Cyanophages' i.e., viruses which attack blue green algae like Lyngbya, Phormidium & Plectonema. They are also called LPP-1 on the basis of hosts. Mycophages were discovered by Sinoten. They contain ds RNA.

Issac & Lindeman discovered a protein called Interferon secreted by host cells against infection of viruses. They selected cold virus for their experiment. Gibbs described viruses in coded form which is called 'Cryptogram of viruses' Cryptogram of viruses is based on 4 pairs of characters:

First pair : Type of nucleic acid in virus i.e. R or D

Number of thread in nucleic acid 1 or 2

Second pair : Molecular weight of viruses in millions i.e. 2

Percentage of nucleic acid of the viruses 5

Third pair : Shape of the virus in total i.e. E (elongeted) or S (spiral) or

X (unknown)

Shape of the protein coat of the virus E or S or X

(E' means elongated structure or rod shaped structure with blunt ends)

Fourth pair : Host/vector i.e. S (seed plant), I(invertebrate), V(vertebrate),

B(bacterium), Fu(fungus), Di(diptra), Af(aphid), Zero or 0 (novector),

X(unknown vector) Vector of the virus X

Thus, for example R/1; 2/5; E/E; S/X is cryptogram of TMV.

For Polia Virus (Poliovirus Primus) cryptogram is R/1; 5/30; S/S; V/O.

For Influenza Virus (mixovirus influenzae) R/1; 2-3/10; S/E; V/O.

For T4 phage D/2; 130/40; X/X; B/O.

2c) Viruses: Some Terms

1. A complete virus having a core of nucleic acid and coat of protein is called virion. Protein coat of the virus is termed as capsid; units of capsid are capsomeres. A virus drops its infective part i.e., nucleic acid alone inside host cell; empty protein coat remains outside. This empty protein coat, which remains outside the host called ghost protein, disappears later on. Raw material for new protein coat of the progeny viruses is contributed by the host.

Þ A few proteins in some viruses are enzymatic in functions e.g. lysozyme in bacteriophages, reverse transcriptase(RNA dependent DNA polymerase) in retrovituses, neuraminidase in influenza virus etc.

2. Viriod: Subviral agent having infectious nucleic acid alone is called viroid. Viroids are RNA & particles lacks protein coat. Spindle disease in photo tuber is caused by viroid, which is PSTV. Viroids were discovered by Diener & Rayner.
3. Prion or Slow Virus: Protein macromolecules causing infections are called prions. They lack ucleic acids. Scrappes & Kuru diseases (Severe brain infection) is sheep are caused by prions. They were first reported by Priusner who was awarded Nobel Prize for reporting Mad Cow disease caused by PrP (prion related protein). Bovine spongiform encephalopathy or Creulzfeldt Jacob disease (a type of insanity in young people), Kuru disease (the laughing death), Alzheimer's disease are caused by prions. In 1976 D.C.Gujdusek was awarded Nobel Prize for his work on prion based diseases.
4. Viruses transmitted by insects are called Arboviruses. Viruses causing Dengue, encephalitis etc are arboviruses.
5. Viruses which contain ss-DNA are called 'Gemini viruses'. ÆX174 phages are geminiviruses. They were reported by Sinsheimer.
6. Viruses which enter inside host cell as intact structures, are called Adeno viruses. Well defined protein coat is absent in Adenoviruses.
7. Virusoids or Satellilte RNAs (Rundle et. Al 1981). These are small circular RNAs similar to viroids, but are located inside the protein coat of a true virus. Virusoids required the assistance of virus for their replication.

2d) Viruses: Classification and Nomenclature

Earlier it was believed that plant viruses i.e. Phytophagineae contain RNA whereas animal viruses i.e. Zoophagineae contain DNA. This is, however, no more correct now. The only thing which is true about viruses is presence of only one type of nucleic acid. Cold virus i.e. Rhinovirus and poliovirus i.e. Enterovirus is together placed under Picorna virus.

2e) Viruses: Disease on Plants – Symptoms

1. Mosaic like spots may develop on leaves.
2. Leaves may show rolling or curling.
3. Leaves may show loss of chlorophyll (Chlorosis) or death of tissues (necrosis).
4. Plants may show abnormal or stunted growth.
5. Plants may show uncontrolled cell division i.e. hyperplasia(cell number increase) and unwanted swelling i.e. Hypertrophy in host.
6. Plants may show loss of entire inflorescence or flowers may become green i.e. virescence in flowers.

2f) Viruses: Some Common Viral Diseases

1. Plant Viral Diseases. Tobacco Mosaic, Potato Mosaic Pumpkin Mosaic, Apple Mosaic, Tulip Mosaic (Broken Tulip), Wheat Mosaic Streak, Bhindi Yellow Vein Mosaic, Potato Leaf Roll, Tobacco Leaf Curl, Papaya Leaf Curl. Banana Bunchy Top, Tomato Bunchy Top, Rice Tungro etc.

2. Animal Viral Diseases. Foot and Mouthm, Enquine encephalitis, Rinderpest, Kysanur Forest Disease (KFD) of monkeys (also humans), New Castle or Ranikhet of Fow].

3. Human Viral Diseases. Poliomyelitis, Rabies, Mumps, Measles, German Measles, Chickenpox, Smallpox (eradicated), Dengue, Encephalitis, Common cold, Flu, some gastrointestinal diseases, Yellow Fever, Herpes, Hepatitis, SARS, AIDS.

MICROBIOLOGY: INTRODUCTION

1. Micro-biology is study of microorganisms like viruses, Bacteria, Protozoa, 1-celled algae and 1-celled fungi etc. Antonie van Leeuwenhoek of Holland, Louis Pasteur of France, Robert Koch of Germany and Joseph Lister of England were earlier, workers in Microbiology. Leeuwenhoek is recognized as 'pioneer' worker in microbiology, he discovered bacteria for the first time as 'animalcules' or the 'wretched beastes'. Pasteur was fist to study role of microorganisms in fermentation process involved in wine preparation. Koch studied anthrax disease, caused by bacteria Bacillus anthracis. On the basis of his study Koch proposed Law of Pathogenicity, which was later on recognized as Koch's Postulates. Koch's Postulates are not applicable for viruses & organisms causing TB and leprosy. Lister introduced antiseptic surgery and also prepared culture of bacteria first time.
2. The two major research institutes of microbiology in world are: Pasteur Institute of Microbiology in Paris, France and Lister Institute of Microbiology, England. Workers at Lister Institute discovered 'naked' bacteria i.e. bacteria without cell of mucopolysaccharide complex. They were called 'L-form' of bacteria, named after Lister Institute. Mycoplasma like organisms, PPLO, is called L-form of Bacteria.
3. Triple Antigen Programme includes, immunization against Diptheria, Pertusis (Whooping cough) and Tetanus. It is also called D.P.T. Oral drops of polio are delivered separately. BCG vaccines are first vaccines given to new borns after 3-4 weeks of birth. Vaccines of: Polio was discovered by Salke; Small pox by Jenner, BCG by Calmett-Guire; Anthrax by Koch and Rabies by Pasteur. Vaccines of anthrax were prepared first. Pasteur, for developing vaccines of rabies was rewarded handsomely by Czar of Russia.