2. INTRODUCTION TO VIROLOGY.

Virology Is the study of viruses.

Viruses are: Viruses are a heterogenous intracellular group of microorganisms. Vary with respect to size, morphology, and chemical composition that contain either deoxyribonucleic acid (DNA) or ribonucleic acid (RNA).

3. Acellular, and metabolically inert outside the host cell. Obligate intracellular parasites No ATP generating system No Ribosomes or means of Protein Synthesis

Typical Virus 1. Nucleic Acid DNA or RNA (But never both) 2. Capsid (Coat Protein) Some Viruses: A. Envelope B. Enzymes

Host range: Host range is determined by Viruses ability to interact with its host cell, Binding Sites should match Receptor Sites Binding Sites - on viral capsid or envelope Receptor Sites - on host cell membrane

Most viruses have a narrow host range: Polio virus - nerve cells Adenovirus - cells in upper Respiratory Tract Some viruses only infect: plants invertebrates protists fungi bacteria (Bacteriophages)

Viral Classification: The classification is depend on 1. Nucleic Acid 2. Morphology 3. Strategy for replication

Viruses are unique life forms different from all other living organisms, either eukaryotes or prokaryotes, for three fundamental reasons: The nature of environment in which they grow and multiply. The nature of their genome. The mode of their multiplication.

First: Viruses can function and multiply only inside another living organism, which may be either a prokaryotic or eukaryotic cell or any other living cells depending on the virus.

Second: Whereas all other living forms can use only DNA (and not RNA) as their genetic material (genome) for information transmission from parent to progeny, viruses can use either DNA or RNA as their genome, that is, some viruses can use only RNA (and not DNA) as their genetic material. Therefore, these classes of RNA viruses have developed new sets of enzymes for replicating and transcribing RNA from an RNA template.

Finally: All eukaryotic and prokaryotic cells divide and multiply as a whole unit, that is, 1 ~ 2 -- 4 ~ 8 and so on. However, viruses do not multiply as a unit. In fact, they have developed a much more efficient way to multiply just as complex machines are made in a modern factory. Different viral components are made separately from independent templates, and then these components are assembled into the whole and infectious units, also called virus particles (virions).

Virions Is the virus particles which consist of two or three parts: the genetic material made from either DNA or RNA, a protein coat that protects these genes; and in some cases an envelope of lipids that surrounds the protein coat when they are outside a cell.

Viral Structure:

DNA or RNA (But never both) 1. Nucleic Acid DNA or RNA (But never both) The nucleic acid is the genome that contains the information necessary for viral function and multiplication. The composition of the protein shell called the viral "nucleocapsid" surrounding the genome. ssDNA - ds DNA - ss RNA - ds RNA

protects viral genome from host endonucleases Capsid (Coat Protein) protects viral genome from host endonucleases Consists of Capsomeres which are structural the units of capsid Contains binding Sites

Derived from the membrane of the host cell. 3- Envelope Derived from the membrane of the host cell. Contains binding Sites The absence of viral membrane gives the naked virus.

Size of viruses: The size of virions ranges from 20 nm (parvovirus) to -300 nm (poxvirus) in diameter, and therefore, too small to be seen with the light microscope. However, it can be studied with the electron microscope, but this microscope is very costly and special training facilities are required to use it.

Shapes of viruses:

1-Helical Meaning the capsid is spiral in shape. It surrounds a spiral shaped core of nucleic acid. Helical capsids are usually flexible and rodlike. The length of the helical capsid is usually determined by the length of the nucleic acids, that is, viruses having shorter nucleic acids will have a shorter helical nucleocapsid. Helical capsids can package only single-stranded RNA, but not double-stranded DNA or RNA, possibly because of the rigidity of the double-stranded nucleic acids.

2- Polyhedral (icosahedral) The term cubic is used to describe Icosahedral viruses. Viruses with icosahedral capsids possess a closed shell enclosing the nucleic acid inside. An icosahedron has 20 triangular faces, 30 edges.

Unlike helical nucleocapsids that package only single-stranded nucleic acid, icosahedral capsids can be used to package either single- or double-stranded RNA and DNA molecules. An icosahedral virus can be either naked or enveloped; but, unlike the helical enveloped viruses, the icosahedron capsid structure is rather rigid.

Complex: Means the capsid symmetry is neither icosahedral nor helical. Only the poxviruses among the medically important viruses show complex symmetry. The overall shape of poxviruses is usually described as brick-shaped.

4-Enveloped Enveloped Helical Enveloped Polyhedral Many of the helical viruses and a few of Icosahedral viruses are surrounded by an envelope.

Dependence of viruses on host cells: Because viruses possess neither cellular structure nor organelles, they are unable to make their own proteins and essential enzymes. They are therefore completely dependent on their host cells for energy and multiplication. Outside of living cells, viruses are metabolically inactive. The information required for a virus to replicate is contained in its nucleic acid. This information is used by the host cell to produce new viruses.

Effect of viruses on cells In animal host the viruses can cause:

1. Cell lyses: The virus leave the host cell by breaking the cytoplasmic membrane and is released out as viroins to attack other cells (enveloped viruses come out of the cells like budding without rupturing the cell.) As the virus comes out of the cell the host cell will rupture i.e lyses (killed) and die.

2. Cell transformation: A small group of viruses are able to change, or transform their host cells from normal cells into abnormal ones with properties of cancerous cells, here the cell is not dead.

3. Immune complex diseases: Immune system of host cell produces antibodies to fight the virus .Antibodies will react with virus (antigen), and Antigen-Antibody complex is produced that deposit in different places of body e.g. Hepatitis B deposit in glomeruli of kidney

4- Asymptomatic Disease: Some viruses after infecting cells do not replicate, or they become active for a time and then become inactive (latent). In response to certain stimuli, latent viruses can be reactivated and become active replicating particles, for example herpesviruses.

CLASSIFICATION OF VIRUSES The internationally agreed system of virus classification is based on the structure and composition of the virus particle (virion). In some cases, the mode of replication is also important in classification. Viruses are classified into various families on this basis.

INTERNATIONAL CLASSIFICATION OF VIRUSES Primary characteristics used in classification: Viruses are classified according to the nature of their genome and their structure

  VIRAL CLASSIFICATION Nucleic acid   RNA or DNA single-stranded or double-stranded non-segmented or segmented linear or circular If genome is single stranded RNA, can it function as mRNA? whether genome is diploid (such as in retroviruses) Virion structure symmetry (icosahedral, helical, complex) enveloped or not enveloped number of capsomers

PRINCIPAL EVENTS INVOLVED IN REPLICATION Adsorption The first step in infection of a cell is attachment to the cell surface. The viral attachment protein recognizes specific receptors, which may be protein, carbohydrate or lipid, on the outside of the cell. Cells without the appropriate receptors are not susceptible to the virus.

Penetration Penetration occurs almost rapidly after attachment and is a next step for gaining entry into the cytoplasm by crossing the plasma membrane. Thus, penetration allows the viruses to deliver their genome into the host cells to initiate replication.

The penetration process differs for different viruses: Penetration by the process of endocytosis is common to both enveloped and non-enveloped viruses. While some virus species can directly penetrate the plasma membrane and inject their genetic material into the cytoplasm, the majority of viruses enter cells via endocytosis. Direct penetration is observed only in non-enveloped viruses, membrane fusion is observed only in enveloped viruses. Some of the non-enveloped viruses like picornaviruses and phages are capable of directly injecting their genome into the host cell.

3-Uncoating: Release of the viral genome from its protective capsid to enable the viral nucleic acid to replicate.  4-Transcription: Synthesis of m-RNA 5-Translation: The viral m-RNA is translated on cell ribosomes into structural and non-structural proteins.

6-Replication of the viral genome 7-Assembly: New virus genomes and proteins are assembled to form new virus particles. 8-Release: -Enveloped viruses are released by budding -Unenveloped viruses are released by rupture and lysis of the infected cells.