PHARMACEUTICAL MICROBIOLOGY JIGAR SHAH INSTITUTE OF PHARMACY NIRMA UNIVERSITY

PHARMACEUTICAL MICROBIOLOGY JIGAR SHAH INSTITUTE OF PHARMACY NIRMA UNIVERSITY

VIRUS - HISTORY In 1886, the Dutch Chemist Adolf Mayer showed TMD In 1892, the Russian Bactriologist Dimtri Iwanowski isolate filterable agents of disease. The first human disease associated with a filterable agent was yellow fever. Described the infectious agent as contagium vivum fluidum a contagious fluid. By the 1930s, scientists had begun using the word VIRUS, the latin word for POISON, to describe these filterable agents. In 1935, Wendell Stanley, an American Chemist, make possible the studies on chemical and structural properties of purified virus by using electron microscope.

Virus History Viruses are found as parasites in all types of organisms, not all of them cause diseases. In 1980s and 1990s, advances in molecular biology techniques have led to the recognition of several new human viruses like HIV, hepatitis C virus, Hantavirus Sin Nombre, and West Nile virus. General Characteristics of Viruses: Viruses are inert outside living host cell, not considered to be living organisms But once viruses enter a host cell, the viral nucleic acids become active, and viral becomes alive & multiplication results. Viruses are especially small (filterable) and obligatory intracellular parasites, they absolutely require living host cells in order to multiply.

Viruses are entities that Virus History - Contain a single type of nucleic acid, either DNA or RNA - Contain a protein coat that surrounds the nucleic acid - Multiply inside living cells by using the synthesizing machinery of the host cell This fact has considerable medical significance for the development of antiviral drugs, because most drugs that would interfere with viral multiplication would also interfere with the functioning of host cell and therefore are too toxic for clinical use - Cause the synthesis of specialized structures that can transfer the viral nucleic acid to other cells - Viruses lack enzymes for protein synthesis and ATP generation

Comparison between Virus and Bacteria Virus History Parameters Bacteria Viruses Typical Bacteria Rickettsias / Chlamydias Intracellular Parasite No Yes Yes Plasma membrane Yes Yes No Binary fission Yes Yes No Pass through bacteriological filter No No / Yes Yes Possess both DNA & RNA Yes Yes No ATP generating metabolism Yes Yes / No No Ribosomes Yes Yes No Sensitive to antibiotics Yes Yes No Sensitive to Interferon No No Yes

Virus History The Host range of a virus is the spectrum of host cells the virus can infect. Viruses can infect invertebrates, vertebrates, plants, protists, fungi and bacteria. Viruses that infect bacteria are called bacteriophages, or phages. The particular host range of a virus is determined by the virus s requirements for its specific attachment to the host cell and the availability of cellular factors required for viral multiplication. For some bacteriophages, the receptor site is part of the cell wall of the host; or part of the fimbriae or flagella For animal viruses, the receptor sites are on the plasma membranes of the host cells.

Virus History The potential to use viruses to treat diseases because of their narrow range and their ability to kill their host cells. The idea of phage theory using bacteriophage to treat bacterial infections. Unfortunately, the immune systems of a treated person or animal quickly eliminates the administered phage. Experimentally induced viral infections in cancer patients suggested that viruses might have antitumor activity. These tumor destroying or oncolytic viruses may selectively infect and kill tumor cells or cause an immune response against tumor cells. Some viruses naturally infect tumor cells and other viruses can be genetically engineered to infect tumor cells. At present several studies are underway to determine the killing mechanism of oncolytic viruses and the safety of using viral therapy.

Viral Size Viral sizes are determined with the aid of electron microscopy. Different viruses vary considerably in size. Although most are quite a bit smaller than bacteria, some of the larger viruses (vaccinia virus) are about the same size as some vary small bacteria (such as the mycoplasmas, rickettsias, chlamydias). Viruses range from 20 to 1000 nm in length.

Viral Structure A VIRION is a complete, fully developed, infectious viral particle composed of nucleic acid and surrounded by a protein coat that protects it from the environment and is a vehicle of transmission from one host cell to another. Viruses are classified by differences in the structures of these coats. Nucleic Acid: In contrast to prokaryotic and eukaryotic cells, in which DNA is always the primary genetic material (and RNA plays an auxiliary role), a virus can have either DNA or RNA, but never both. The nucleic acid of a virus can be single-stranded or doublestranded. Thus, there are viruses with the familiar double stranded DNA, with single stranded DNA, with double stranded RNA, and with single stranded RNA.

Viral Structure Depending on the virus, the nucleic acid can be linear or circular or in several separate segments (influenza virus). The percentage of nucleic acid in relation to proteins is about 1% (influenzavirus) and about 50% for certain bacteriophages Total amount of nucleic acid varies from thousand nucleotides to 250,000 nucleotides. (E. coli consists 4 million nucleotide pairs). Capsid & Envelope: Protein coat is known as Capsid. Each capsid is composed of protein subunits called capsomeres. Some viruses the proteins composing the single type capsomeres, in others may be several types of capsomeres Individual capsomeres are visible in electron micrographs The arrangement of capsomeres is characteristic of a particular type of virus.

Viral Structure In some viruses, the capsid is covered by an envelope, which consists of combination of lipids, proteins and carbohydrates. Depending on virus, envelopes may or may not be covered by spikes, which are carbohydrate-protein complexes that project from the surface of the envelope. Some viruses attach to host cell by means of spikes. Spikes are such a reliable characteristic as means of identification of some viruses. Spikes of Influenzavirus has ability to clump red blood cells, bind with them and form bridges between them. The resulting clumping is called hemagglutination, and is the basis for several useful laboratory tests.

Viral Structure Viruses whose capsid are not covered by an envelope are known as nonenveloped viruses. The capsid of this type of virus protects the nucleic acid from nucleus enzymes in biological fluids and promotes the virus s attachment to susceptible host cells. The progeny of mutant virus e.g. influenzavirus General Morphology: Classification into different morphological types based on their capsid architecture which has been revealed by electron microscopy and a technique called X-ray crystallography. Helical Viruses: - Long rods, rigid or flexible - Nucleic acid is found within a hollow, cylindrical capsid - They cause rabies and Ebola hemorrhagic fever

Polyhedral Viruses: Viral Structure - Many animal, plant and bacterial viruses are polyhedral or many sided viruses. - Capsid is in the shape of an icosahedron, a regular polyhedron with 20 triangular faces and 12 corners. - The capsomeres of each face form an equilateral trianglel. - E.g. adenovirus, poliovirus. Enveloped viruses: - Spherical - When helical or polyhedral viruses are enclosed by envelopes, they are called enveloped helical or enveloped polyhedral viruses. - E.g. of enveloped helical virus is influenzavirus & of enveloped polyhedral virus is herpes simplex virus

Complex Virus: Viral Structure - Have complicated structure, particularly bacterial viruses - E.g. Bacteriophage, Poxviruses. Here, capsid (head polyhedral) contains additional structures like tail sheath (helical), tail fibres, plate, and pin.